Astrocyte Dysfunctions in Obsessive Compulsive Disorder: Rethinking Neurobiology and Therapeutic Targets.
Details
Serval ID
serval:BIB_B14759715279
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Astrocyte Dysfunctions in Obsessive Compulsive Disorder: Rethinking Neurobiology and Therapeutic Targets.
Journal
Journal of neurochemistry
ISSN
1471-4159 (Electronic)
ISSN-L
0022-3042
Publication state
Published
Issued date
05/2025
Peer-reviewed
Oui
Volume
169
Number
5
Pages
e70092
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Publication Status: ppublish
Abstract
Obsessive-compulsive disorder (OCD) has long been conceptualized as a neuron-centric disorder of cortico-striato-thalamo-cortical (CSTC) circuit dysregulation. However, a growing body of evidence is now reframing this narrative, placing astrocytes-once relegated to passive support roles-at the center of OCD pathophysiology. Astrocytes are critical regulators of glutamate and GABA homeostasis, calcium signaling, and synaptic plasticity, all of which are disrupted in OCD. Recent high-resolution molecular and proteomic studies reveal that specific astrocyte subpopulations, including Crym-positive astrocytes, directly shape excitatory/inhibitory balance and control perseverative behaviors by modulating presynaptic inputs from the orbitofrontal cortex. Disruptions in astrocytic neurotransmitter clearance and dopamine metabolism amplify CSTC circuit hyperactivity and reinforce compulsions. This review reframes OCD as a disorder of neuro-glial dysfunctions, proposing that targeting astrocytic signaling, metabolism, and structural plasticity may unlock transformative therapeutic strategies. By integrating human and animal data, we advocate for a glial-centric model of OCD that not only enhances mechanistic understanding but also opens new frontiers for precision treatment.
Keywords
Humans, Astrocytes/metabolism, Astrocytes/drug effects, Astrocytes/pathology, Obsessive-Compulsive Disorder/metabolism, Obsessive-Compulsive Disorder/physiopathology, Obsessive-Compulsive Disorder/drug therapy, Obsessive-Compulsive Disorder/therapy, Obsessive-Compulsive Disorder/pathology, Animals, Neuronal Plasticity/physiology, Neurobiology, OCD, astrocytes, psychiatric disorders
Pubmed
Open Access
Yes
Create date
27/05/2025 16:37
Last modification date
28/05/2025 7:09