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Bu sayfa, 26. Dünya Psikiyatri Kongresi'nde sunulan çalışmanın yapay zekâ desteğiyle hazırlanmış Türkçe özetidir. Çalışmanın sahibi sunan yazarlardır; atıf için orijinal kaynağa başvurun.

EV0817

The L-PGDS/15d-PGJ2/CRTH2 axis causes synaptic impairment in depression by regulating astrocyte–neuron crosstalk

THE L-PGDS/15D-PGJ2/CRTH2 AXIS DRIVES SYNAPTIC IMPAIRMENT IN DEPRESSION BY REGULATING ASTROCYTE-NEURON CROSSTALK

Plasma 15d-PGJ2 levels are elevated in major depressive disorder, and the astrocyte-derived L-PGDS/15d-PGJ2/CRTH2 signaling axis in the amygdala mediates depression-like behaviors and synaptic impairment.

The aim is to elucidate the cellular mechanisms of impaired synaptic plasticity in major depressive disorder (MDD) by examining the role of the L-PGDS/15d-PGJ2/CRTH2 axis in astrocyte–neuron crosstalk in the amygdala. The methods included untargeted metabolomic sequencing of plasma from patients with MDD, followed by molecular biological validation of the brain regions and cell types showing 15d-PGJ2 accumulation in the chronic social defeat stress (CSDS) mouse model of depression. Genes upstream and downstream in the pathway were then silenced or overexpressed using genetic tools. Behavioral assessments included the social interaction test (SIT), sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST). The findings showed a significant increase in prostaglandin J2 in the MDD group (fold change = 1.995; p = 3.89 × 10^-5). Plasma 15d-PGJ2 levels were higher in patients than in controls and positively correlated with HAMD-24 scores; no significant difference in plasma levels was detected between women and men (ns). Administration of 15d-PGJ2 (0.01 mg/kg) into the amygdala induced depression-like behaviors in mice, as measured by the SPT, TST, and FST. In the CSDS model, upregulation of L-PGDS in amygdala astrocytes increased the pathological accumulation of 15d-PGJ2, while administration of AZD1981 and GW9662 (2 mg/kg/day, i.p.) improved behavioral outcomes; CRTH2 mRNA levels were elevated in stress-susceptible animals compared with controls. In conclusion, the study identifies a mechanistic link between disrupted lipid metabolism and neuronal dysfunction, suggesting that this axis may be explored for biomarker development and targeted treatment in MDD.

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