An Astroglial Basis of Major Depressive Disorder: Molecular, Cellular, and Circuit Features

• Published in: Biological psychiatry (1969) Vol. 97; no. 3; pp. 217 - 226
• Main Authors: Lu, Cheng-Lin, Ren, Jing, Cao, Xiong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2025
• Subjects: Animals; Astrocyte network; Astrocyte-neuron crosstalk; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Blood-Brain Barrier - metabolism; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brainwide network; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - pathology; Depressive Disorder, Major - physiopathology; Glutamic Acid - metabolism; Humans; Major depressive disorder; Psychiatric/Mental Health; Stress; Brainwide network; Astrocyte-neuron crosstalk; Astrocyte network; Astrocytes; Major depressive disorder; Stress; glucocorticoid receptor; KYNA; Resting-state functional connectivity; BBB; basic fibroblast growth factor; CUMS; quinolinic acid; Brain-wide network; glial-derived neurotrophic factor; kynurenine; rsFC; MDD; PFC; locus coeruleus; S100 calcium-binding protein B; purinergic receptor P2X; TRP; Cx; hypothalamus-pituitary-adrenal; purinergic ligand-gated ion channel 7 receptor; P2X2; brain-derived neurotrophic factor; S100β; lateral habenula; KYN; O-GlcNAc transferase; hamilton depression scale; monocarboxylate transporter 4; connexins; bFGF; ligand-gated ion channel; 2; NOD-like receptor thermal protein domain associated protein; cerebrospinal fluid; HPA; GPCR; inositol 1,4,5-trisphosphate receptor; glial fibrillary acidic protein; kynurenic acid; chronic unpredictable mild stress; IP3R; CRS; prefrontal cortex; chronic social defeat stress; 3-HK; P2X7R; MCT4; rsfMRI; glutamate transporter-1; CSF; NLRP; Resting-state functional magnetic resonance imaging; tryptophan; blood-brain barrier; CSDS; G protein-coupled receptor; ACC; Anterior cingulate cortex; BDNF; LHb; chronic restraint stress; GR; GFAP; QUIN; 3-hydroxykynurenine; HAMD; GDNF; LC; OGT; GLT-1
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2024.07.017

Major depressive disorder is a common psychiatric disorder and a leading cause of disability worldwide. Astrocytes play a role in the maintenance of the function of the central nervous system, both physiologically and pathologically. Accumulated evidence indicates that the astrocyte is an important contributor to the pathophysiology of major depressive disorder including blood-brain barrier integrity, gap junctions, gliotransmission, glutamate homeostasis, and energy metabolism. Here, we comprehensively summarize an astroglial basis for major depressive disorder based on molecular, cellular, and circuit properties, suggesting that astrocytes appear to be highly sensitive to stress and are likely to be uniquely positioned to integrate peripheral and central stress responses.