Astrocytes in depression and Alzheimer’s disease

doi:10.1007/s11684-021-0875-0

Front. Med.

2021, Vol. 15

Issue (6) : 829-841 https://doi.org/10.1007/s11684-021-0875-0

REVIEW

Astrocytes in depression and Alzheimer’s disease

Yang Liao¹, Qu Xing², Qianqian Li³, Jing Zhang¹, Ruiyuan Pan¹(

), Zengqiang Yuan¹(

)

¹. The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China
². School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China
³. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

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Abstract

Astrocytes are an abundant subgroup of cells in the central nervous system (CNS) that play a critical role in controlling neuronal circuits involved in emotion, learning, and memory. In clinical cases, multiple chronic brain diseases may cause psychosocial and cognitive impairment, such as depression and Alzheimer’s disease (AD). For years, complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability, resulting in gradual loss of self-care ability, lower life qualities, and vast burden on human society. Interestingly, correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease. As a kind of multifunctional glial cell in the CNS, astrocytes maintain physiological function via supporting neuronal cells, modulating pathologic niche, and regulating energy metabolism. Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD. We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD, with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.

Keywords astrocytes depression Alzheimer’s disease roles mechanisms

Corresponding Author(s): Ruiyuan Pan,Zengqiang Yuan

Just Accepted Date: 09 November 2021 Online First Date: 23 November 2021 Issue Date: 27 December 2021

Cite this article:

Yang Liao,Qu Xing,Qianqian Li, et al. Astrocytes in depression and Alzheimer’s disease[J]. Front. Med., 2021, 15(6): 829-841.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0875-0
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I6/829

Fig.1 Diagram of ANLS in depression. Astrocytes take up glucose from the capillary via GLUT1, store it by converting it into glycogen, or catabolize it into pyruvate by glycolysis. Pyruvate can be converted into lactate, which is then delivered into neurons through MCTs. The uptake of astrocyte-derived lactate by neurons is converted to pyruvate. Glucose from the capillary can also be absorbed in neurons via GLUTs and is then catabolized into pyruvate, which is fed into the TCA cycle for energy production and participates in synaptic plasticity and depression development. MCTs, monocarboxylate transporters; GLUT, glucose transporter; TCA, tricarboxylic acid cycle.

Fig.2 Astrocyte-derived ATP plays a dual role in neuronal function. Due to the significantly different receptor affinities in normal circumstances (P2X2 is100-fold>P2X7), ATP released from homeostatic astrocytes serves as a neurotransmitter or neuromodulator, which binds with P2X2R in neurons, maintaining neuronal morphology, excitability, and plasticity. By contrast, when astrocytes are activated under pathological conditions, they produce excessive ATP, binding with P2X7 in microglia, followed in sequence by the upregulation of NLRP3 and caspase-1, release of IL-1β, and finally neuroinflammation and neurotoxicity.

Fig.3 Summary of this review. Astrocytes modulate extracellular ATP, neuroinflammation, and energy metabolism in the progression of depression. In addition, astrocytes regulate the above physiologic processes and Aβ aggregation and tau protein hyperphosphorylation in the pathology of AD. The multiple roles of astrocytes in depression and AD might link depression and AD. Increasing evidence showed that depression is thought to be a risk factor or prodrome of AD. Aβ, amyloid-β.

1	A Araque, V Parpura, RP Sanzgiri, PG Haydon. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 1999; 22(5): 208–215 https://doi.org/10.1016/S0166-2236(98)01349-6 pmid: 10322493
2	A Volterra, J Meldolesi. Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 2005; 6(8): 626–640 https://doi.org/10.1038/nrn1722 pmid: 16025096
3	E Blanco-Suárez, AL Caldwell, NJ Allen. Role of astrocyte-synapse interactions in CNS disorders. J Physiol 2017; 595(6): 1903–1916 https://doi.org/10.1113/JP270988 pmid: 27381164
4	BS Khakh, MV Sofroniew. Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci 2015; 18(7): 942–952 https://doi.org/10.1038/nn.4043 pmid: 26108722
5	JA Stogsdill, J Ramirez, D Liu, YH Kim, KT Baldwin, E Enustun, T Ejikeme, RR Ji, C Eroglu. Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis. Nature 2017; 551(7679): 192–197 https://doi.org/10.1038/nature24638 pmid: 29120426
6	BS Khakh. Astrocyte-neuron interactions in the striatum: insights on identity, form, and function. Trends Neurosci 2019; 42(9): 617–630 https://doi.org/10.1016/j.tins.2019.06.003 pmid: 31351745
7	M Campisi, Y Shin, T Osaki, C Hajal, V Chiono, RD Kamm. 3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes. Biomaterials 2018; 180: 117–129 https://doi.org/10.1016/j.biomaterials.2018.07.014 pmid: 30032046
8	SA Liddelow, SE Marsh, B Stevens. Microglia and astrocytes in disease: dynamic duo or partners in crime? Trends Immunol 2020; 41(9): 820–835 https://doi.org/10.1016/j.it.2020.07.006 pmid: 32819809
9	GS Alexopoulos. Depression in the elderly. Lancet 2005; 365(9475): 1961–1970 https://doi.org/10.1016/S0140-6736(05)66665-2 pmid: 15936426
10	R Cui. Editorial: a systematic review of depression. Curr Neuropharmacol 2015; 13(4): 480 https://doi.org/10.2174/1570159X1304150831123535 pmid: 26412067
11	B Gaynes. Assessing the risk factors for difficult-to-treat depression and treatment-resistant depression. J Clin Psychiatry 2016; 77(Suppl 1): 4–8 https://doi.org/10.4088/JCP.14077su1c.01 pmid: 26829431
12	J Wang, X Wu, W Lai, E Long, X Zhang, W Li, Y Zhu, C Chen, X Zhong, Z Liu, D Wang, H Lin. Prevalence of depression and depressive symptoms among outpatients: a systematic review and meta-analysis. BMJ Open 2017; 7(8): e017173 https://doi.org/10.1136/bmjopen-2017-017173 pmid: 28838903
13	World Health Organization. Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization, 2017
14	GS Malhi, JJ Mann. Depression. Lancet 2018; 392(10161): 2299–2312 https://doi.org/10.1016/S0140-6736(18)31948-2 pmid: 30396512
15	S Boku, S Nakagawa, H Toda, A Hishimoto. Neural basis of major depressive disorder: beyond monoamine hypothesis. Psychiatry Clin Neurosci 2018; 72(1): 3–12 https://doi.org/10.1111/pcn.12604 pmid: 28926161
16	DJ David, AM Gardier. The pharmacological basis of the serotonin system: application to antidepressant response. Encephale 2016; 42(3): 255–263 (in French) https://doi.org/10.1016/j.encep.2016.03.012 pmid: 27112704
17	G Oxenkrug. Serotonin-kynurenine hypothesis of depression: historical overview and recent developments. Curr Drug Targets 2013; 14(5): 514–521 https://doi.org/10.2174/1389450111314050002 pmid: 23514379
18	S Takahashi. Reduction of blood platelet serotonin levels in manic and depressed patients. Folia Psychiatr Neurol Jpn 1976; 30(4): 475–486 https://doi.org/10.1111/j.1440-1819.1976.tb02670.x pmid: 1021543
19	PS Rojas, JL Fiedler. What do we really know about 5-HT1A receptor signaling in neuronal cells? Front Cell Neurosci 2016; 10: 272 https://doi.org/10.3389/fncel.2016.00272 pmid: 27932955
20	CM Teixeira, ZB Rosen, D Suri, Q Sun, M Hersh, D Sargin, I Dincheva, AA Morgan, S Spivack, AC Krok, T Hirschfeld-Stoler, EK Lambe, SA Siegelbaum, MS Ansorge. Hippocampal 5-HT input regulates memory formation and Schaffer collateral excitation. Neuron 2018; 98(5): 992–1004.e4 https://doi.org/10.1016/j.neuron.2018.04.030 pmid: 29754752
21	MI Naharci, O Buyukturan, U Cintosun, H Doruk, I Tasci. Functional status of older adults with dementia at the end of life: is there still anything to do? Indian J Palliat Care 2019; 25(2): 197–202 https://doi.org/10.4103/IJPC.IJPC_156_18 pmid: 31114103
22	Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 2016; 12(4): 459–509 https://doi.org/10.1016/j.jalz.2016.03.001 pmid: 27570871
23	J Jia, C Wei, S Chen, F Li, Y Tang, W Qin, L Zhao, H Jin, H Xu, F Wang, A Zhou, X Zuo, L Wu, Y Han, Y Han, L Huang, Q Wang, D Li, C Chu, L Shi, M Gong, Y Du, J Zhang, J Zhang, C Zhou, J Lv, Y Lv, H Xie, Y Ji, F Li, E Yu, B Luo, Y Wang, S Yang, Q Qu, Q Guo, F Liang, J Zhang, L Tan, L Shen, K Zhang, J Zhang, D Peng, M Tang, P Lv, B Fang, L Chu, L Jia, S Gauthier. The cost of Alzheimer’s disease in China and re-estimation of costs worldwide. Alzheimers Dement 2018; 14(4): 483–491 https://doi.org/10.1016/j.jalz.2017.12.006 pmid: 29433981
24	RY Pan, J Ma, XX Kong, XF Wang, SS Li, XL Qi, YH Yan, J Cheng, Q Liu, W Jin, CH Tan, Z Yuan. Sodium rutin ameliorates Alzheimer’s disease-like pathology by enhancing microglial amyloid-β clearance. Sci Adv 2019; 5(2): eaau6328 https://doi.org/10.1126/sciadv.aau6328 pmid: 30820451
25	O Realdon, F Rossetto, M Nalin, I Baroni, M Cabinio, R Fioravanti, FL Saibene, M Alberoni, F Mantovani, M Romano, R Nemni, F Baglio. Technology-enhanced multi-domain at home continuum of care program with respect to usual care for people with cognitive impairment: the Ability-TelerehABILITation study protocol for a randomized controlled trial. BMC Psychiatry 2016; 16(1): 425 https://doi.org/10.1186/s12888-016-1132-y pmid: 27887597
26	SH Barage, KD Sonawane. Amyloid cascade hypothesis: pathogenesis and therapeutic strategies in Alzheimer’s disease. Neuropeptides 2015; 52: 1–18 https://doi.org/10.1016/j.npep.2015.06.008 pmid: 26149638
27	EN Cline, MA Bicca, KL Viola, WL Klein. The amyloid-β oligomer hypothesis: beginning of the third decade. J Alzheimers Dis 2018; 64(s1): S567–S610 https://doi.org/10.3233/JAD-179941 pmid: 29843241
28	DJ Selkoe, J Hardy. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8(6): 595–608 https://doi.org/10.15252/emmm.201606210 pmid: 27025652
29	L Bakota, R Brandt. Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs 2016; 76(3): 301–313 https://doi.org/10.1007/s40265-015-0529-0 pmid: 26729186
30	B Eftekharzadeh, JG Daigle, LE Kapinos, A Coyne, J Schiantarelli, Y Carlomagno, C Cook, SJ Miller, S Dujardin, AS Amaral, JC Grima, RE Bennett, K Tepper, M DeTure, CR Vanderburg, BT Corjuc, SL DeVos, JA Gonzalez, J Chew, S Vidensky, FH Gage, J Mertens, J Troncoso, E Mandelkow, X Salvatella, RYH Lim, L Petrucelli, S Wegmann, JD Rothstein, BT Hyman. Tau protein disrupts nucleocytoplasmic transport in Alzheimer’s disease. Neuron 2018; 99(5): 925–940.e7 https://doi.org/10.1016/j.neuron.2018.07.039 pmid: 30189209
31	SS Mirza, FJ Wolters, SA Swanson, PJ Koudstaal, A Hofman, H Tiemeier, MA Ikram. 10-year trajectories of depressive symptoms and risk of dementia: a population-based study. Lancet Psychiatry 2016; 3(7): 628–635 https://doi.org/10.1016/S2215-0366(16)00097-3 pmid: 27138970
32	AD Burke, D Goldfarb, P Bollam, S Khokher. Diagnosing and treating depression in patients with Alzheimer’s disease. Neurol Ther 2019; 8(2): 325–350 https://doi.org/10.1007/s40120-019-00148-5 pmid: 31435870
33	F Novais, S Starkstein. Phenomenology of depression in Alzheimer’s disease. J Alzheimers Dis 2015; 47(4): 845–855 https://doi.org/10.3233/JAD-148004 pmid: 26401763
34	JA Cobb, K O’Neill, J Milner, GJ Mahajan, TJ Lawrence, WL May, J Miguel-Hidalgo, G Rajkowska, CA Stockmeier. Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder. Neuroscience 2016; 316: 209–220 https://doi.org/10.1016/j.neuroscience.2015.12.044 pmid: 26742791
35	L Lemoine, L Saint-Aubert, I Nennesmo, PG Gillberg, A Nordberg. Cortical laminar tau deposits and activated astrocytes in Alzheimer’s disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography. Sci Rep 2017; 7(1): 45496 https://doi.org/10.1038/srep45496 pmid: 28374768
36	AM Arranz, B De Strooper. The role of astroglia in Alzheimer’s disease: pathophysiology and clinical implications. Lancet Neurol 2019; 18(4): 406–414 https://doi.org/10.1016/S1474-4422(18)30490-3 pmid: 30795987
37	C Escartin, O Guillemaud, MA Carrillo-de Sauvage. Questions and (some) answers on reactive astrocytes. Glia 2019; 67(12): 2221–2247 https://doi.org/10.1002/glia.23687 pmid: 31429127
38	C Howarth, P Gleeson, D Attwell. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab 2012; 32(7): 1222–1232 https://doi.org/10.1038/jcbfm.2012.35 pmid: 22434069
39	CM Alberini, E Cruz, G Descalzi, B Bessières, V Gao. Astrocyte glycogen and lactate: new insights into learning and memory mechanisms. Glia 2018; 66(6): 1244–1262 https://doi.org/10.1002/glia.23250 pmid: 29076603
40	C Giaume, A Koulakoff, L Roux, D Holcman, N Rouach. Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat Rev Neurosci 2010; 11(2): 87–99 https://doi.org/10.1038/nrn2757 pmid: 20087359
41	H Koepsell. Glucose transporters in brain in health and disease. Pflugers Arch 2020; 472(9): 1299–1343 https://doi.org/10.1007/s00424-020-02441-x pmid: 32789766
42	C Calì, A Tauffenberger, P Magistretti. The strategic location of glycogen and lactate: from body energy reserve to brain plasticity. Front Cell Neurosci 2019; 13: 82 https://doi.org/10.3389/fncel.2019.00082 pmid: 30894801
43	PJ Magistretti, I Allaman. Lactate in the brain: from metabolic end-product to signalling molecule. Nat Rev Neurosci 2018; 19(4): 235–249 https://doi.org/10.1038/nrn.2018.19 pmid: 29515192
44	SC Cunnane, E Trushina, C Morland, A Prigione, G Casadesus, ZB Andrews, MF Beal, LH Bergersen, RD Brinton, S de la Monte, A Eckert, J Harvey, R Jeggo, JH Jhamandas, O Kann, CM la Cour, WF Martin, G Mithieux, PI Moreira, MP Murphy, KA Nave, T Nuriel, SHR Oliet, F Saudou, MP Mattson, RH Swerdlow, MJ Millan. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov 2020; 19(9): 609–633 https://doi.org/10.1038/s41573-020-0072-x pmid: 32709961
45	I Juaristi, L Contreras, P González-Sánchez, I Pérez-Liébana, L González-Moreno, B Pardo, A Del Arco, J Satrústegui. The response to stimulation in neurons and astrocytes. Neurochem Res 2019; 44(10): 2385–2391 https://doi.org/10.1007/s11064-019-02803-7 pmid: 31016552
46	LF Barros, A Brown, RA Swanson. Glia in brain energy metabolism: a perspective. Glia 2018; 66(6): 1134–1137 https://doi.org/10.1002/glia.23316 pmid: 29476554
47	GA Dienel. Brain glucose metabolism: integration of energetics with function. Physiol Rev 2019; 99(1): 949–1045 https://doi.org/10.1152/physrev.00062.2017 pmid: 30565508
48	P Mächler, MT Wyss, M Elsayed, J Stobart, R Gutierrez, A von Faber-Castell, V Kaelin, M Zuend, A San Martín, I Romero-Gómez, F Baeza-Lehnert, S Lengacher, BL Schneider, P Aebischer, PJ Magistretti, LF Barros, B Weber. In vivo evidence for a lactate gradient from astrocytes to neurons. Cell Metab 2016; 23(1): 94–102 https://doi.org/10.1016/j.cmet.2015.10.010 pmid: 26698914
49	A Suzuki, SA Stern, O Bozdagi, GW Huntley, RH Walker, PJ Magistretti, CM Alberini. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 2011; 144(5): 810–823 https://doi.org/10.1016/j.cell.2011.02.018 pmid: 21376239
50	GA Brooks. The science and translation of lactate shuttle theory. Cell Metab 2018; 27(4): 757–785 https://doi.org/10.1016/j.cmet.2018.03.008 pmid: 29617642
51	J Detka, A Kurek, M Kucharczyk, K Głombik, A Basta-Kaim, M Kubera, W Lasoń, B Budziszewska. Brain glucose metabolism in an animal model of depression. Neuroscience 2015; 295: 198–208 https://doi.org/10.1016/j.neuroscience.2015.03.046 pmid: 25819664
52	YN Yin, J Hu, YL Wei, ZL Li, ZC Luo, RQ Wang, KX Yang, SJ Li, XW Li, JM Yang, TM Gao. Astrocyte-derived lactate modulates the passive coping response to behavioral challenge in male mice. Neurosci Bull 2021; 37(1): 1–14 https://doi.org/10.1007/s12264-020-00553-z pmid: 32785834
53	C Murphy-Royal, AD Johnston, AKJ Boyce, B Diaz-Castro, A Institoris, G Peringod, O Zhang, RF Stout, DC Spray, RJ Thompson, BS Khakh, JS Bains, GR Gordon. Stress gates an astrocytic energy reservoir to impair synaptic plasticity. Nat Commun 2020; 11(1): 2014 https://doi.org/10.1038/s41467-020-15778-9 pmid: 32332733
54	A Carrard, M Elsayed, M Margineanu, B Boury-Jamot, L Fragnière, EM Meylan, JM Petit, H Fiumelli, PJ Magistretti, JL Martin. Peripheral administration of lactate produces antidepressant-like effects. Mol Psychiatry 2018; 23(2): 392–399 https://doi.org/10.1038/mp.2016.179 pmid: 27752076
55	J Yang, E Ruchti, JM Petit, P Jourdain, G Grenningloh, I Allaman, PJ Magistretti. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci USA 2014; 111(33): 12228–12233 https://doi.org/10.1073/pnas.1322912111 pmid: 25071212
56	CL Powell, AR Davidson, AM Brown. Universal glia to neurone lactate transfer in the nervous system: physiological functions and pathological consequences. Biosensors (Basel) 2020; 10(11): E183 https://doi.org/10.3390/bios10110183 pmid: 33228235
57	N Karnib, R El-Ghandour, L El Hayek, P Nasrallah, M Khalifeh, N Barmo, V Jabre, P Ibrahim, M Bilen, JS Stephan, EB Holson, RR Ratan, SF Sleiman. Lactate is an antidepressant that mediates resilience to stress by modulating the hippocampal levels and activity of histone deacetylases. Neuropsychopharmacology 2019; 44(6):1152–1162 https://doi.org/10.1038/s41386-019-0313-z pmid: 30647450
58	LK Bak, AB Walls. CrossTalk opposing view: lack of evidence supporting an astrocyte-to-neuron lactate shuttle coupling neuronal activity to glucose utilisation in the brain. J Physiol 2018; 596(3): 351–353 https://doi.org/10.1113/JP274945 pmid: 29292507
59	GA Dienel. Lack of appropriate stoichiometry: strong evidence against an energetically important astrocyte-neuron lactate shuttle in brain. J Neurosci Res 2017; 95(11): 2103–2125 https://doi.org/10.1002/jnr.24015 pmid: 28151548
60	F Lipmann. Metabolic Generation and Utilization of Phosphate Bond Energy. John Wiley & Sons, Inc., 2006
61	M Mori, C Heuss, BH Gähwiler, U Gerber. Fast synaptic transmission mediated by P2X receptors in CA3 pyramidal cells of rat hippocampal slice cultures. J Physiol 2001; 535(1): 115–123 https://doi.org/10.1111/j.1469-7793.2001.t01-1-00115.x pmid: 11507162
62	Y Pankratov, U Lalo, O Krishtal, A Verkhratsky. Ionotropic P2X purinoreceptors mediate synaptic transmission in rat pyramidal neurones of layer II/III of somato-sensory cortex. J Physiol 2002; 542(2): 529–536 https://doi.org/10.1113/jphysiol.2002.021956 pmid: 12122150
63	X Cao, LP Li, Q Wang, Q Wu, HH Hu, M Zhang, YY Fang, J Zhang, SJ Li, WC Xiong, HC Yan, YB Gao, JH Liu, XW Li, LR Sun, YN Zeng, XH Zhu, TM Gao. Astrocyte-derived ATP modulates depressive-like behaviors. Nat Med 2013; 19(6): 773–777 https://doi.org/10.1038/nm.3162 pmid: 23644515
64	Y Bansal, A Kuhad. Mitochondrial dysfunction in depression. Curr Neuropharmacol 2016; 14(6): 610–618 https://doi.org/10.2174/1570159X14666160229114755 pmid: 26923778
65	Y Nakamura, JH Park, K Hayakawa. Therapeutic use of extracellular mitochondria in CNS injury and disease. Exp Neurol 2020; 324: 113114 https://doi.org/10.1016/j.expneurol.2019.113114 pmid: 31734316
66	P Illes, P Rubini, H Yin, Y Tang. Impaired ATP release from brain astrocytes may be a cause of major depression. Neurosci Bull 2020; 36(11): 1281–1284 https://doi.org/10.1007/s12264-020-00494-7 pmid: 32279193
67	V Rajani, Y Zhang, V Jalubula, V Rancic, S SheikhBahaei, JD Zwicker, S Pagliardini, CT Dickson, K Ballanyi, S Kasparov, AV Gourine, GD Funk. Release of ATP by pre-Bötzinger complex astrocytes contributes to the hypoxic ventilatory response via a Ca2+-dependent P2Y1 receptor mechanism. J Physiol 2018; 596(15): 3245–3269 https://doi.org/10.1113/JP274727 pmid: 28678385
68	MM Halassa, T Fellin, PG Haydon. Tripartite synapses: roles for astrocytic purines in the control of synaptic physiology and behavior. Neuropharmacology 2009; 57(4): 343–346 https://doi.org/10.1016/j.neuropharm.2009.06.031 pmid: 19577581
69	W Cai, C Xue, M Sakaguchi, M Konishi, A Shirazian, HA Ferris, ME Li, R Yu, A Kleinridders, EN Pothos, CR Kahn. Insulin regulates astrocyte gliotransmission and modulates behavior. J Clin Invest 2018; 128(7): 2914–2926 https://doi.org/10.1172/JCI99366 pmid: 29664737
70	W Choi, N Clemente, W Sun, J Du, W Lü. The structures and gating mechanism of human calcium homeostasis modulator 2. Nature 2019; 576(7785): 163–167 https://doi.org/10.1038/s41586-019-1781-3 pmid: 31776515
71	JL Syrjanen, K Michalski, TH Chou, T Grant, S Rao, N Simorowski, SJ Tucker, N Grigorieff, H Furukawa. Structure and assembly of calcium homeostasis modulator proteins. Nat Struct Mol Biol 2020; 27(2): 150–159 https://doi.org/10.1038/s41594-019-0369-9 pmid: 31988524
72	J Ma, X Qi, C Yang, R Pan, S Wang, J Wu, L Huang, H Chen, J Cheng, R Wu, Y Liao, L Mao, FC Wang, Z Wu, JX An, Y Wang, X Zhang, C Zhang, Z Yuan. Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors. Mol Psychiatry 2018; 23(4): 883–891 https://doi.org/10.1038/mp.2017.229 pmid: 29180673
73	U Dreses-Werringloer, JC Lambert, V Vingtdeux, H Zhao, H Vais, A Siebert, A Jain, J Koppel, A Rovelet-Lecrux, D Hannequin, F Pasquier, D Galimberti, E Scarpini, D Mann, C Lendon, D Campion, P Amouyel, P Davies, JK Foskett, F Campagne, P Marambaud. A polymorphism in CALHM1 influences Ca2+ homeostasis, Aβ levels, and Alzheimer’s disease risk. Cell 2008; 133(7): 1149–1161 https://doi.org/10.1016/j.cell.2008.05.048 pmid: 18585350
74	A Taruno, V Vingtdeux, M Ohmoto, Z Ma, G Dvoryanchikov, A Li, L Adrien, H Zhao, S Leung, M Abernethy, J Koppel, P Davies, MM Civan, N Chaudhari, I Matsumoto, G Hellekant, MG Tordoff, P Marambaud, JK Foskett. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 2013; 495(7440): 223–226 https://doi.org/10.1038/nature11906 pmid: 23467090
75	D Rial, C Lemos, H Pinheiro, JM Duarte, FQ Gonçalves, JI Real, RD Prediger, N Gonçalves, CA Gomes, PM Canas, P Agostinho, RA Cunha. Depression as a glial-based synaptic dysfunction. Front Cell Neurosci 2016; 9: 521 https://doi.org/10.3389/fncel.2015.00521 pmid: 26834566
76	A Trautmann. Extracellular ATP in the immune system: more than just a “danger signal”. Sci Signal 2009; 2(56): pe6 https://doi.org/10.1126/scisignal.256pe6 pmid: 19193605
77	L Janks, CVR Sharma, TM Egan. A central role for P2X7 receptors in human microglia. J Neuroinflammation 2018; 15(1): 325 https://doi.org/10.1186/s12974-018-1353-8 pmid: 30463629
78	M Iwata, KT Ota, XY Li, F Sakaue, N Li, S Dutheil, M Banasr, V Duric, T Yamanashi, K Kaneko, K Rasmussen, A Glasebrook, A Koester, D Song, KA Jones, S Zorn, G Smagin, RS Duman. Psychological stress activates the inflammasome via release of adenosine triphosphate and stimulation of the purinergic type 2X7 receptor. Biol Psychiatry 2016; 80(1): 12–22 https://doi.org/10.1016/j.biopsych.2015.11.026 pmid: 26831917
79	P Illes, A Verkhratsky, Y Tang. Pathological ATPergic signaling in major depression and bipolar disorder. Front Mol Neurosci 2020; 12: 331 https://doi.org/10.3389/fnmol.2019.00331 pmid: 32076399
80	RK Farooq, A Tanti, S Ainouche, S Roger, C Belzung, V Camus. A P2X7 receptor antagonist reverses behavioural alterations, microglial activation and neuroendocrine dysregulation in an unpredictable chronic mild stress (UCMS) model of depression in mice. Psychoneuroendocrinology 2018; 97: 120–130 https://doi.org/10.1016/j.psyneuen.2018.07.016 pmid: 30015007
81	N Yue, H Huang, X Zhu, Q Han, Y Wang, B Li, Q Liu, G Wu, Y Zhang, J Yu. Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors. J Neuroinflammation 2017; 14(1): 102 https://doi.org/10.1186/s12974-017-0865-y pmid: 28486969
82	RJ Rodrigues, AR Tomé, RA Cunha. ATP as a multi-target danger signal in the brain. Front Neurosci 2015; 9: 148 https://doi.org/10.3389/fnins.2015.00148 pmid: 25972780
83	C Wang, Q Yin, Z Su, L. Xia Progress on role of extracellular ATP and its metabolite adenosine in immunoregulation: review. Chin J Cell Mol Immunol (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) 2020; 36(12):1134–1140 (in Chinese)
84	M Schain, WC Kreisl. Neuroinflammation in neurodegenerative disorders—a review. Curr Neurol Neurosci Rep 2017; 17(3): 25 https://doi.org/10.1007/s11910-017-0733-2 pmid: 28283959
85	T Shabab, R Khanabdali, SZ Moghadamtousi, HA Kadir, G Mohan. Neuroinflammation pathways: a general review. Int J Neurosci 2017; 127(7): 624–633 https://doi.org/10.1080/00207454.2016.1212854 pmid: 27412492
86	E Colombo, C Farina. Astrocytes: key regulators of neuroinflammation. Trends Immunol 2016; 37(9): 608–620 https://doi.org/10.1016/j.it.2016.06.006 pmid: 27443914
87	JR Faulkner, JE Herrmann, MJ Woo, KE Tansey, NB Doan, MV Sofroniew. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004; 24(9): 2143–2155 https://doi.org/10.1523/JNEUROSCI.3547-03.2004 pmid: 14999065
88	DJ Myer, GG Gurkoff, SM Lee, DA Hovda, MV Sofroniew. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 2006; 129(10): 2761–2772 https://doi.org/10.1093/brain/awl165 pmid: 16825202
89	RR Voskuhl, RS Peterson, B Song, Y Ao, LB Morales, S Tiwari-Woodruff, MV Sofroniew. Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 2009; 29(37): 11511–11522 https://doi.org/10.1523/JNEUROSCI.1514-09.2009 pmid: 19759299
90	L Mayo, SA Trauger, M Blain, M Nadeau, B Patel, JI Alvarez, ID Mascanfroni, A Yeste, P Kivisäkk, K Kallas, B Ellezam, R Bakshi, A Prat, JP Antel, HL Weiner, FJ Quintana. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med 2014; 20(10): 1147–1156 https://doi.org/10.1038/nm.3681 pmid: 25216636
91	D Brites, A Fernandes. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci 2015; 9: 476 https://doi.org/10.3389/fncel.2015.00476 pmid: 26733805
92	R Troubat, P Barone, S Leman, T Desmidt, A Cressant, B Atanasova, B Brizard, W El Hage, A Surget, C Belzung, V Camus. Neuroinflammation and depression: a review. Eur J Neurosci 2021; 53(1): 151–171 https://doi.org/10.1111/ejn.14720 pmid: 32150310
93	A Cernackova, Z Durackova, J Trebaticka, B Mravec. Neuroinflammation and depressive disorder: the role of the hypothalamus. J Clin Neurosci 2020; 75: 5–10 https://doi.org/10.1016/j.jocn.2020.03.005 pmid: 32217047
94	ZH Zheng, JL Tu, XH Li, Q Hua, WZ Liu, Y Liu, BX Pan, P Hu, WH Zhang. Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala. Brain Behav Immun 2021; 91: 505–518 https://doi.org/10.1016/j.bbi.2020.11.007 pmid: 33161163
95	T Ali, SU Rahman, Q Hao, W Li, Z Liu, F Ali Shah, I Murtaza, Z Zhang, X Yang, G Liu, S Li. Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation. J Pineal Res 2020; 69(2): e12667 https://doi.org/10.1111/jpi.12667 pmid: 32375205
96	W Li, T Ali, K He, Z Liu, FA Shah, Q Ren, Y Liu, A Jiang, S Li. Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression. Brain Behav Immun 2021; 92: 10–24 pmid: 33181270
97	AK Walker, EE Wing, WA Banks, R Dantzer. Leucine competes with kynurenine for blood-to-brain transport and prevents lipopolysaccharide-induced depression-like behavior in mice. Mol Psychiatry 2019; 24(10): 1523–1532 https://doi.org/10.1038/s41380-018-0076-7 pmid: 29988087
98	Y Zhang, L Du, Y Bai, B Han, C He, L Gong, R Huang, L Shen, J Chao, P Liu, H Zhang, H Zhang, L Gu, J Li, G Hu, C Xie, Z Zhang, H Yao. CircDYM ameliorates depressive-like behavior by targeting miR-9 to regulate microglial activation via HSP90 ubiquitination. Mol Psychiatry 2020; 25(6): 1175–1190 https://doi.org/10.1038/s41380-018-0285-0 pmid: 30413800
99	L Leng, K Zhuang, Z Liu, C Huang, Y Gao, G Chen, H Lin, Y Hu, D Wu, M Shi, W Xie, H Sun, Z Shao, H Li, K Zhang, W Mo, TY Huang, M Xue, Z Yuan, X Zhang, G Bu, H Xu, Q Xu, J Zhang. Menin deficiency leads to depressive-like behaviors in mice by modulating astrocyte-mediated neuroinflammation. Neuron 2018; 100(3): 551–563.e7 https://doi.org/10.1016/j.neuron.2018.08.031 pmid: 30220511
100	Y Wu, A Qiu, Z Yang, J Wu, X Li, K Bao, M Wang, B Wu. Malva sylvestris extract alleviates the astrogliosis and inflammatory stress in LPS-induced depression mice. J Neuroimmunol 2019; 336: 577029 https://doi.org/10.1016/j.jneuroim.2019.577029 pmid: 31487612
101	Y Wang, J Ni, L Zhai, C Gao, L Xie, L Zhao, X Yin. Inhibition of activated astrocyte ameliorates lipopolysaccharide-induced depressive-like behaviors. J Affect Disord 2019; 242: 52–59 https://doi.org/10.1016/j.jad.2018.08.015 pmid: 30172225
102	HY Zhang, Y Wang, Y He, T Wang, XH Huang, CM Zhao, L Zhang, SW Li, C Wang, YN Qu, XX Jiang. A1 astrocytes contribute to murine depression-like behavior and cognitive dysfunction, which can be alleviated by IL-10 or fluorocitrate treatment. J Neuroinflammation 2020; 17(1): 200 https://doi.org/10.1186/s12974-020-01871-9 pmid: 32611425
103	ER Zimmer, A Leuzy, AL Benedet, J Breitner, S Gauthier, P Rosa-Neto. Tracking neuroinflammation in Alzheimer’s disease: the role of positron emission tomography imaging. J Neuroinflammation 2014; 11(1): 120 https://doi.org/10.1186/1742-2094-11-120 pmid: 25005532
104	GR Frost, YM Li. The role of astrocytes in amyloid production and Alzheimer’s disease. Open Biol 2017; 7(12): 170228 https://doi.org/10.1098/rsob.170228 pmid: 29237809
105	F Panza, M Lozupone, G Logroscino, BP Imbimbo. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol 2019; 15(2): 73–88 https://doi.org/10.1038/s41582-018-0116-6 pmid: 30610216
106	A Verkhratsky, V Parpura, JJ Rodriguez-Arellano, R Zorec. Astroglia in Alzheimer’s disease. Adv Exp Med Biol 2019; 1175: 273–324 https://doi.org/10.1007/978-981-13-9913-8_11 pmid: 31583592
107	A Serrano-Pozo, A Muzikansky, T Gómez-Isla, JH Growdon, RA Betensky, MP Frosch, BT Hyman. Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease. J Neuropathol Exp Neurol 2013; 72(6): 462–471 https://doi.org/10.1097/NEN.0b013e3182933788 pmid: 23656989
108	Y Okabe, T Takahashi, C Mitsumasu, K Kosai, E Tanaka, T Matsuishi. Alterations of gene expression and glutamate clearance in astrocytes derived from an MeCP2-null mouse model of Rett syndrome. PLoS One 2012; 7(4): e35354 https://doi.org/10.1371/journal.pone.0035354 pmid: 22532851
109	A Tagarelli, A Piro, G Tagarelli, P Lagonia, A Quattrone. Alois Alzheimer: a hundred years after the discovery of the eponymous disorder. Int J Biomed Sci 2006; 2(2): 196–204 pmid: 23674983
110	MH Ahmad, M Fatima, AC Mondal. Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer’s disease: rational insights for the therapeutic approaches. J Clin Neurosci 2019; 59: 6–11 https://doi.org/DOI: 10.1016/j.jocn.2018.10.034 pmid: 30385170
111	SF Carter, K Herholz, P Rosa-Neto, L Pellerin, A Nordberg, ER Zimmer. Astrocyte biomarkers in Alzheimer’s disease. Trends Mol Med 2019; 25(2): 77–95 https://doi.org/10.1016/j.molmed.2018.11.006 pmid: 30611668
112	S Li, M Jin, T Koeglsperger, NE Shepardson, GM Shankar, DJ Selkoe. Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci 2011; 31(18): 6627–6638 https://doi.org/10.1523/JNEUROSCI.0203-11.2011 pmid: 21543591
113	SA Liddelow, KA Guttenplan, LE Clarke, FC Bennett, CJ Bohlen, L Schirmer, ML Bennett, AE Münch, WS Chung, TC Peterson, DK Wilton, A Frouin, BA Napier, N Panicker, M Kumar, MS Buckwalter, DH Rowitch, VL Dawson, TM Dawson, B Stevens, BA Barres. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017; 541(7638): 481–487 https://doi.org/10.1038/nature21029 pmid: 28099414
114	S Rossner, C Lange-Dohna, U Zeitschel, JR Perez-Polo. Alzheimer’s disease β-secretase BACE1 is not a neuron-specific enzyme. J Neurochem 2005; 92(2): 226–234 https://doi.org/10.1111/j.1471-4159.2004.02857.x pmid: 15663471
115	K Veeraraghavalu, C Zhang, X Zhang, RE Tanzi, SS Sisodia. Age-dependent, non-cell-autonomous deposition of amyloid from synthesis of β-amyloid by cells other than excitatory neurons. J Neurosci 2014; 34(10): 3668–3673 https://doi.org/10.1523/JNEUROSCI.5079-13.2014 pmid: 24599465
116	CA Brunello, M Merezhko, RL Uronen, HJ Huttunen. Mechanisms of secretion and spreading of pathological tau protein. Cell Mol Life Sci 2020; 77(9): 1721–1744 https://doi.org/10.1007/s00018-019-03349-1 pmid: 31667556
117	Y Gao, L Tan, JT Yu, L Tan. Tau in Alzheimer’s disease: mechanisms and therapeutic strategies. Curr Alzheimer Res 2018; 15(3): 283–300 https://doi.org/10.2174/1567205014666170417111859 pmid: 28413986
118	R van der Kant, LSB Goldstein, R Ossenkoppele. Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci 2020; 21(1): 21–35 https://doi.org/10.1038/s41583-019-0240-3 pmid: 31780819
119	GG Kovacs. Astroglia and tau: new perspectives. Front Aging Neurosci 2020; 12: 96 https://doi.org/10.3389/fnagi.2020.00096 pmid: 32327993
120	M Allen, X Wang, DJ Serie, SL Strickland, JD Burgess, S Koga, CS Younkin, TT Nguyen, KG Malphrus, SJ Lincoln, M Alamprese, K Zhu, R Chang, MM Carrasquillo, N Kouri, ME Murray, JS Reddy, C Funk, ND Price, TE Golde, SG Younkin, YW Asmann, JE Crook, DW Dickson, N Ertekin-Taner. Divergent brain gene expression patterns associate with distinct cell-specific tau neuropathology traits in progressive supranuclear palsy. Acta Neuropathol 2018; 136(5): 709–727 https://doi.org/10.1007/s00401-018-1900-5 pmid: 30136084
121	L Buée, T Bussière, V Buée-Scherrer, A Delacourte, PR Hof. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 2000; 33(1): 95–130 https://doi.org/10.1016/S0165-0173(00)00019-9 pmid: 10967355
122	SJ Adams, MA DeTure, M McBride, DW Dickson, L Petrucelli. Three repeat isoforms of tau inhibit assembly of four repeat tau filaments. PLoS One 2010; 5(5): e10810 https://doi.org/10.1371/journal.pone.0010810 pmid: 20520830
123	K Richetin, P Steullet, M Pachoud, R Perbet, E Parietti, M Maheswaran, S Eddarkaoui, S Bégard, C Pythoud, M Rey, R Caillierez, K Q Do, S Halliez, P Bezzi, L Buée, G Leuba, M Colin, N Toni, N Déglon. Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease. Nat Neurosci 2020; 23(12): 1567–1579 https://doi.org/10.1038/s41593-020-00728-x pmid: 33169029
124	TJ Bussian, A Aziz, CF Meyer, BL Swenson, JM van Deursen, DJ Baker. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 2018; 562(7728): 578–582 https://doi.org/10.1038/s41586-018-0543-y pmid: 30232451
125	JT Newington, RA Harris, RC Cumming. Reevaluating metabolism in Alzheimer’s disease from the perspective of the astrocyte-neuron lactate shuttle model. J Neurodegener Dis 2013; 2013: 234572 https://doi.org/10.1155/2013/234572 pmid: 26316984
126	M Zhang, X Cheng, R Dang, W Zhang, J Zhang, Z Yao. Lactate deficit in an Alzheimer disease mouse model: the relationship with neuronal damage. J Neuropathol Exp Neurol 2018; 77(12): 1163–1176 https://doi.org/10.1093/jnen/nly102 pmid: 30383244
127	S Pal, S Paul. ATP controls the aggregation of Aβ16-22 peptides. J Phys Chem B 2020; 124(1): 210–223 https://doi.org/10.1021/acs.jpcb.9b10175 pmid: 31830415
128	ES Jung, K An, HS Hong, JH Kim, I Mook-Jung. Astrocyte-originated ATP protects Aβ(1-42)-induced impairment of synaptic plasticity. J Neurosci 2012; 32(9): 3081–3087 https://doi.org/10.1523/JNEUROSCI.6357-11.2012 pmid: 22378880
129	JC Park, SH Han, I Mook-Jung. Peripheral inflammatory biomarkers in Alzheimer’s disease: a brief review. BMB Rep 2020; 53(1): 10–19 https://doi.org/10.5483/BMBRep.2020.53.1.309 pmid: 31865964
130	MT Heneka, MJ Carson, J El Khoury, GE Landreth, F Brosseron, DL Feinstein, AH Jacobs, T Wyss-Coray, J Vitorica, RM Ransohoff, K Herrup, SA Frautschy, B Finsen, GC Brown, A Verkhratsky, K Yamanaka, J Koistinaho, E Latz, A Halle, GC Petzold, T Town, D Morgan, ML Shinohara, VH Perry, C Holmes, NG Bazan, DJ Brooks, S Hunot, B Joseph, N Deigendesch, O Garaschuk, E Boddeke, CA Dinarello, JC Breitner, GM Cole, DT Golenbock, MP Kummer. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015; 14(4): 388–405 https://doi.org/10.1016/S1474-4422(15)70016-5 pmid: 25792098
131	M Fakhoury. Microglia and astrocytes in Alzheimer’s disease: implications for therapy. Curr Neuropharmacol 2018; 16(5): 508–518 https://doi.org/10.2174/1570159X15666170720095240 pmid: 28730967
132	CF Pereira, AE Santos, PI Moreira, AC Pereira, FJ Sousa, SM Cardoso, MT Cruz. Is Alzheimer’s disease an inflammasomopathy? Ageing Res Rev 2019; 56: 100966 https://doi.org/10.1016/j.arr.2019.100966 pmid: 31577960
133	D Kaur, V Sharma, R Deshmukh. Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease. Inflammopharmacology 2019; 27(4): 663–677 https://doi.org/10.1007/s10787-019-00580-x pmid: 30874945
134	JL Furman, DM Sama, JC Gant, TL Beckett, MP Murphy, AD Bachstetter, LJ Van Eldik, CM Norris. Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer’s disease. J Neurosci 2012; 32(46): 16129–16140 https://doi.org/10.1523/JNEUROSCI.2323-12.2012 pmid: 23152597
135	L Katsouri, AM Birch, AWJ Renziehausen, C Zach, Y Aman, H Steeds, A Bonsu, EOC Palmer, N Mirzaei, M Ries, M Sastre. Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer’s disease. Glia 2020; 68(5): 1017–1030 https://doi.org/10.1002/glia.23759 pmid: 31799735
136	X Shu, Y Sun, X Sun, Y Zhou, Y Bian, Z Shu, J Ding, M Lu, G Hu. The effect of fluoxetine on astrocyte autophagy flux and injured mitochondria clearance in a mouse model of depression. Cell Death Dis 2019; 10(8): 577 https://doi.org/10.1038/s41419-019-1813-9 pmid: 31371719
137	P Belujon, AA Grace. Dopamine system dysregulation in major depressive disorders. Int J Neuropsychopharmacol 2017; 20(12): 1036–1046 https://doi.org/10.1093/ijnp/pyx056 pmid: 29106542
138	I Koppel, K Jaanson, A Klasche, J Tuvikene, T Tiirik, A Pärn, T Timmusk. Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation. Glia 2018; 66(1): 206–216 https://doi.org/10.1002/glia.23238 pmid: 28983964
139	W Shao, SZ Zhang, M Tang, XH Zhang, Z Zhou, YQ Yin, QB Zhou, YY Huang, YJ Liu, E Wawrousek, T Chen, SB Li, M Xu, JN Zhou, G Hu, JW Zhou. Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin. Nature 2013; 494(7435): 90–94 https://doi.org/10.1038/nature11748 pmid: 23242137
140	M Shimizu, A Nishida, H Zensho, S Yamawaki. Chronic antidepressant exposure enhances 5-hydroxytryptamine7 receptor-mediated cyclic adenosine monophosphate accumulation in rat frontocortical astrocytes. J Pharmacol Exp Ther 1996; 279(3): 1551–1558 pmid: 8968382
141	PM Whitaker-Azmitia, C Clarke, EC Azmitia. Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action. Synapse 1993; 14(3): 201–205 https://doi.org/10.1002/syn.890140303 pmid: 8211706
142	M Corkrum, A Covelo, J Lines, L Bellocchio, M Pisansky, K Loke, R Quintana, PE Rothwell, R Lujan, G Marsicano, ED Martin, MJ Thomas, P Kofuji, A Araque. Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity. Neuron 2020; 105(6): 1036–1047.e5 https://doi.org/10.1016/j.neuron.2019.12.026 pmid: 31954621
143	M Inazu, H Takeda, H Ikoshi, M Sugisawa, Y Uchida, T Matsumiya. Pharmacological characterization and visualization of the glial serotonin transporter. Neurochem Int 2001; 39(1): 39–49 https://doi.org/10.1016/S0197-0186(01)00010-9 pmid: 11311448
144	X Zhou, Q Xiao, L Xie, F Yang, L Wang, J Tu. Astrocyte, a promising target for mood disorder interventions. Front Mol Neurosci 2019; 12: 136 https://doi.org/10.3389/fnmol.2019.00136 pmid: 31231189
145	M Kinoshita, Y Hirayama, K Fujishita, K Shibata, Y Shinozaki, E Shigetomi, A Takeda, HPN Le, H Hayashi, M Hiasa, Y Moriyama, K Ikenaka, KF Tanaka, S Koizumi. Anti-depressant fluoxetine reveals its therapeutic effect via astrocytes. EBioMedicine 2018; 32: 72–83 https://doi.org/10.1016/j.ebiom.2018.05.036 pmid: 29887330
146	YM Park, BH Lee. Alterations in serum BDNF and GDNF levels after 12 weeks of antidepressant treatment in female outpatients with major depressive disorder. Psychiatry Investig 2018; 15(8): 818–823 https://doi.org/10.30773/pi.2018.03.31 pmid: 29945425
147	M Niwa, A Nitta, Y Yamada, A Nakajima, K Saito, M Seishima, L Shen, Y Noda, S Furukawa, T Nabeshima. An inducer for glial cell line-derived neurotrophic factor and tumor necrosis factor-α protects against methamphetamine-induced rewarding effects and sensitization. Biol Psychiatry 2007; 61(7): 890–901 https://doi.org/10.1016/j.biopsych.2006.06.016 pmid: 17046726
148	L Lu, X Wang, P Wu, C Xu, M Zhao, M Morales, BK Harvey, BJ Hoffer, Y Shaham. Role of ventral tegmental area glial cell line-derived neurotrophic factor in incubation of cocaine craving. Biol Psychiatry 2009; 66(2): 137–145 https://doi.org/10.1016/j.biopsych.2009.02.009 pmid: 19345340
149	JR Fisher, CE Wallace, DL Tripoli, YI Sheline, JR Cirrito. Redundant Gs-coupled serotonin receptors regulate amyloid-β metabolism in vivo. Mol Neurodegener 2016; 11(1): 45 https://doi.org/10.1186/s13024-016-0112-5 pmid: 27315796
150	J Ma, Y Gao, L Jiang, FL Chao, W Huang, CN Zhou, W Tang, L Zhang, CX Huang, Y Zhang, YM Luo, Q Xiao, HR Yu, R Jiang, Y Tang. Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer’s disease mice. Oncotarget 2017; 8(17): 27676–27692 https://doi.org/10.18632/oncotarget.15398 pmid: 28430602
151	CN Zhou, FL Chao, Y Zhang, L Jiang, L Zhang, JH Fan, YX Wu, XY Dou, Y Tang. Fluoxetine delays the cognitive function decline and synaptic changes in a transgenic mouse model of early Alzheimer’s disease. J Comp Neurol 2019; 527(8): 1378–1387 https://doi.org/10.1002/cne.24616 pmid: 30592045
152	GS Alexopoulos. Mechanisms and treatment of late-life depression. Transl Psychiatry 2019; 9(1): 188 https://doi.org/10.1038/s41398-019-0514-6 pmid: 31383842
153	AA Grace. Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat Rev Neurosci 2016; 17(8): 524–532 https://doi.org/10.1038/nrn.2016.57 pmid: 27256556
154	K Pytka, K Podkowa, A Rapacz, A Podkowa, E Żmudzka, A Olczyk, J Sapa, B Filipek. The role of serotonergic, adrenergic and dopaminergic receptors in antidepressant-like effect. Pharmacol Rep 2016; 68(2): 263–274 https://doi.org/10.1016/j.pharep.2015.08.007 pmid: 26922526
155	U Kumar, SC Patel. Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer’s disease brain. Brain Res 2007; 1131(1): 187–196 https://doi.org/10.1016/j.brainres.2006.10.049 pmid: 17182012
156	X Pan, AC Kaminga, SW Wen, X Wu, K Acheampong, A Liu. Dopamine and dopamine receptors in Alzheimer’s disease: a systematic review and network meta-analysis. Front Aging Neurosci 2019; 11: 175 https://doi.org/10.3389/fnagi.2019.00175 pmid: 31354471
157	G Koch, F Di Lorenzo, S Bonnì, V Giacobbe, M Bozzali, C Caltagirone, A Martorana. Dopaminergic modulation of cortical plasticity in Alzheimer’s disease patients. Neuropsychopharmacology. 2014; 39(11): 2654–2661 https://doi.org/10.1038/npp.2014.119 pmid: 24859851
158	M D’Amelio, S Puglisi-Allegra, N Mercuri. The role of dopaminergic midbrain in Alzheimer’s disease: translating basic science into clinical practice. Pharmacol Res 2018; 130: 414–419 https://doi.org/10.1016/j.phrs.2018.01.016 pmid: 29391234
159	P Krashia, A Nobili, M D’Amelio. Unifying hypothesis of dopamine neuron loss in neurodegenerative diseases: focusing on Alzheimer’s disease. Front Mol Neurosci 2019; 12: 123 https://doi.org/10.3389/fnmol.2019.00123 pmid: 31156387
160	MK Jha, M Jo, JH Kim, K Suk. Microglia-astrocyte crosstalk: an intimate molecular conversation. Neuroscientist 2019; 25(3): 227–240 https://doi.org/10.1177/1073858418783959 pmid: 29931997
161	AV Molofsky, B Deneen. Astrocyte development: a guide for the perplexed. Glia 2015; 63(8): 1320–1329 https://doi.org/10.1002/glia.22836 pmid: 25963996
162	J Herbert, PJ Lucassen. Depression as a risk factor for Alzheimer’s disease: genes, steroids, cytokines and neurogenesis—what do we need to know? Front Neuroendocrinol 2016; 41: 153–171 https://doi.org/10.1016/j.yfrne.2015.12.001 pmid: 26746105
163	RL Ownby, E Crocco, A Acevedo, V John, D Loewenstein. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry 2006; 63(5): 530–538 https://doi.org/10.1001/archpsyc.63.5.530 pmid: 16651510
164	K Barlinn, J Kepplinger, V Puetz, BM Illigens, U Bodechtel, T Siepmann. Exploring the risk-factor association between depression and incident stroke: a systematic review and meta-analysis. Neuropsychiatr Dis Treat 2014; 11: 1–14 https://doi.org/10.2147/NDT.S63904 pmid: 25565846
165	Y Gan, Y Gong, X Tong, H Sun, Y Cong, X Dong, Y Wang, X Xu, X Yin, J Deng, L Li, S Cao, Z Lu. Depression and the risk of coronary heart disease: a meta-analysis of prospective cohort studies. BMC Psychiatry 2014; 14(1): 371 https://doi.org/10.1186/s12888-014-0371-z pmid: 25540022
166	R Troubat, P Barone, S Leman, T Desmidt, A Cressant, B Atanasova, B Brizard, W El Hage, A Surget, C Belzung, V Camus. Neuroinflammation and depression: a review. Eur J Neurosci 2021; 53(1): 151–171 pmid: 32150310
167	MS Uddin, MT Kabir, MS Rahman, T Behl, P Jeandet, GM Ashraf, A Najda, MN Bin-Jumah, HR El-Seedi, MM Abdel-Daim. Revisiting the amyloid cascade hypothesis: from anti-Aβ therapeutics to auspicious new ways for Alzheimer’s disease. Int J Mol Sci 2020; 21(16): E5858 https://doi.org/10.3390/ijms21165858 pmid: 32824102
168	Q Wang, W Jie, JH Liu, JM Yang, TM Gao. An astroglial basis of major depressive disorder? An overview. Glia 2017; 65(8): 1227–1250 https://doi.org/10.1002/glia.23143 pmid: 28317185
169	X Han, M Chen, F Wang, M Windrem, S Wang, S Shanz, Q Xu, NA Oberheim, L Bekar, S Betstadt, AJ Silva, T Takano, SA Goldman, M Nedergaard. Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 2013; 12(3): 342–353 https://doi.org/10.1016/j.stem.2012.12.015 pmid: 23472873
170	AC Lepore, B Rauck, C Dejea, AC Pardo, MS Rao, JD Rothstein, NJ Maragakis. Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci 2008; 11(11): 1294–1301 https://doi.org/10.1038/nn.2210 pmid: 18931666
171	H Qian, X Kang, J Hu, D Zhang, Z Liang, F Meng, X Zhang, Y Xue, R Maimon, SF Dowdy, NK Devaraj, Z Zhou, WC Mobley, DW Cleveland, XD Fu. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 2020; 582(7813): 550–556 https://doi.org/10.1038/s41586-020-2388-4 pmid: 32581380
172	H Zhou, J Su, X Hu, C Zhou, H Li, Z Chen, Q Xiao, B Wang, W Wu, Y Sun, Y Zhou, C Tang, F Liu, L Wang, C Feng, M Liu, S Li, Y Zhang, H Xu, H Yao, L Shi, H Yang. Glia-to-neuron conversion by CRISPR-CasRx alleviates symptoms of neurological disease in mice. Cell 2020; 181(3): 590–603.e16 https://doi.org/10.1016/j.cell.2020.03.024 pmid: 32272060

[1]	Liping Xuan, Zhiyun Zhao, Xu Jia, Yanan Hou, Tiange Wang, Mian Li, Jieli Lu, Yu Xu, Yuhong Chen, Lu Qi, Weiqing Wang, Yufang Bi, Min Xu. Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis[J]. Front. Med., 2018, 12(6): 678-687.
[2]	Han Wang, Hong Zhou, Yan Zhang, Yan Wang, Jing Sun. Association of maternal depression with dietary intake, growth, and development of preterm infants: a cohort study in Beijing, China[J]. Front. Med., 2018, 12(5): 533-541.
[3]	Isabel Andia, Michele Abate. Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions[J]. Front. Med., 2018, 12(2): 139-152.
[4]	Li LI, Jianxin JIANG. Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction mechanisms[J]. Front Med, 2011, 5(1): 33-39.

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