Astroglia and depression: A Gliocentric perspective from rodent models to therapeutic insights.
Progress in neuro-psychopharmacology & biological psychiatry January 27, 2026 Rhea Subba, Surendar Ellappan, Sugato Banerjee et al.
Astroglial dysfunction is a fundamental component of the pathophysiology of major depressive disorder. Rodent models of depression consistently show structural astroglial abnormalities, including atrophy in the prefrontal cortex and hippocampus, reduced glial fibrillary acidic protein expression, impaired glutamate homeostasis, decreased neurotrophic factor production, disrupted gap junction communication, diminished lactate release, increased neuroinflammation, and synaptic deficits. Clinical postmortem and serum biomarker studies corroborate astroglial dysfunction in cortical regions of patients with MDD. Standard antidepressants (SSRIs, SNRIs, tricyclics, serotonin modulators) and rapid-acting ones like ketamine and esketamine exert therapeutic effects at least partially by restoring astroglial homeostasis, positioning astroglia as critical mediators of treatment response and a promising target for personalized antidepressant strategies.