Increased forebrain EAAT3 expression confers resilience to chronic stress
Depression is a disabling and highly prevalent psychiatric illness. Multiple studies have linked glutamatergic dysfunction with the pathophysiology of depression, but the exact alterations in the glutamatergic system that contribute to depressive-like behaviors are not fully understood. Recent evide...
Gespeichert in:
Veröffentlicht in: | Journal of neurochemistry 2025-01, Vol.169 (1), p.e16216 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Depression is a disabling and highly prevalent psychiatric illness. Multiple studies have linked glutamatergic dysfunction with the pathophysiology of depression, but the exact alterations in the glutamatergic system that contribute to depressive-like behaviors are not fully understood. Recent evidence suggests that a decreased level in neuronal glutamate transporter (EAAT3), known to control glutamate levels and limit the activation of glutamate receptors at synaptic sites, may contribute to the manifestation of a depressive phenotype. Here, we tested the possibility that increased EAAT3 expression at excitatory synapses could reduce the susceptibility of mice to develop depressive-like behaviors when challenged to a 5-week unpredictable chronic mild stress (UCMS) protocol. Mice overexpressing EAAT3 in the forebrain (EAAT3
/CMKII) and control littermates (EAAT3
) were assessed for depressive-like behaviors and long-term memory performance after being subjected to UCMS conditions. We found that, after UCMS, EAAT3
/CMKII mice did not exhibit depressive-like behaviors or memory alterations observed in control mice. Moreover, we found that EAAT3
/CMKII mice did not show alterations in phasic dopamine release in the nucleus accumbens neither in long-term synaptic plasticity in the CA1 region of the hippocampus after UCMS, as observed in control littermates. Altogether these results suggest that forebrain EAAT3 overexpression may be related to a resilient phenotype, both at behavioral and functional level, to the deleterious effect of chronic stress, highlighting the importance of neuronal EAAT3 in the pathophysiology of depressive-like behaviors. |
---|---|
ISSN: | 0022-3042 1471-4159 1471-4159 |
DOI: | 10.1111/jnc.16216 |