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...

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Veröffentlicht in:Journal of neurochemistry 2025-01, Vol.169 (1), p.e16216
Hauptverfasser: Ardiles, Nicolás M, Tapia-Cuevas, Vissente, Estay, Sebastián F, Alcaino, Alejandro, Velásquez, Victoria B, Sotomayor-Zárate, Ramón, Chávez, Andrés E, Moya, Pablo R
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Sprache:eng
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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