ß-Catenin Role in the Vulnerability/Resilience to Stress-Related Disorders Is Associated to Changes in the Serotonergic System.
Mol Neurobiol
; 57(3): 1704-1715, 2020 Mar.
Article
em En
| MEDLINE
| ID: mdl-31823197
ABSTRACT
We previously reported that the inactivation (cKO) or the stabilization (cST) of ß-catenin in cells expressing the astrocyte-specific glutamate aspartate transporter (GLAST) is associated with the vulnerability or resilience to exhibit anxious/depressive-like behaviors, respectively, and to changes in hippocampal proliferation. Here, we used these cKO and cST ß-catenin mice to study the serotonergic system functionality associated with their behavioral/molecular phenotype. The activity of 5-HT1A receptors was assessed by (+)-8-OH-DPAT-induced hypothermia and [35S]GTPγS binding autoradiography. The animals' response to acute stress and the levels of extracellular serotonin (5-HT) in the medial prefrontal cortex (mPFC) were also assessed. cKO mice presented higher 5-HT1A autoreceptor functionality, lower 5-HT1A heteroreceptor functionality, and a decrease in extracellular 5-HT levels in the mPFC. These neurochemical changes were accompanied with a blunted physiological response to stress-induced hyperthermia. In contrast, cST mice showed a reduced 5-HT1A autoreceptor functionality and higher extracellular 5-HT levels in the mPFC after fluoxetine administration. Moreover, cST mice subjected to chronic corticosterone administration did not show a blunted response to fluoxetine. Our findings suggest the existence of a link between ß-catenin levels and 5-HT1A receptor functionality, which may be relevant to understand the neurobiological bases underlying the vulnerability or resilience to stress-related disorders.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
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Serotonina
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Receptor 5-HT1A de Serotonina
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Beta Catenina
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article