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ß-Catenin Role in the Vulnerability/Resilience to Stress-Related Disorders Is Associated to Changes in the Serotonergic System

Abstract: We previously reported that the inactivation (cKO) or the stabilization (cST) of ?-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 ?-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]GTP?S 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 ?-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.

 Fuente: Mol Neurobiol , 57 (3), 1704-1715 Mar 2020

 Publisher: Springer

 Year of publication: 2020

 No. of pages: 12

 Publication type: Article

 DOI: 10.1007/s12035-019-01841-0

 ISSN: 0893-7648,1559-1182

 Spanish project: SAF2011-25020 ; SAF2015-67457-R

 Publication Url: https://doi.org/10.1007/s12035-019-01841-0