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1.
Neurochem Res ; 48(7): 2175-2186, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36853481

RESUMEN

Activating transcription factor 6 (ATF6) is an endoplasmic reticulum (ER) stress-regulated transcription factor that induces expression of major molecular chaperones in the ER. We recently reported that ATF6ß, a subtype of ATF6, promoted survival of hippocampal neurons exposed to ER stress and excitotoxicity, at least in part by inducing expression of calreticulin, an ER molecular chaperone with high Ca2+-binding capacity. In the present study, we demonstrate that ATF6ß deficiency in mice also decreases calreticulin expression and increases expression of glucose-regulated protein 78, another ER molecular chaperone, in emotional brain regions such as the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala. Comprehensive behavioral analyses revealed that Atf6b-/- mice exhibit anxiety-like behavior in the light/dark transition test and hyperactivity in the forced swim test. Consistent with these results, PFC and hypothalamic corticotropin-releasing hormone (CRH) expression was increased in Atf6b-/- mice, as was circulating corticosterone. Moreover, CRH receptor 1 antagonism alleviated anxiety-like behavior in Atf6b-/- mice. These findings suggest that ATF6ß deficiency produces anxiety-like behavior and hyperactivity via a CRH receptor 1-dependent mechanism. ATF6ß could play a role in psychiatric conditions in the emotional centers of the brain.


Asunto(s)
Calreticulina , Receptores de Hormona Liberadora de Corticotropina , Ratones , Animales , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Calreticulina/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Hipotálamo/metabolismo , Ansiedad/metabolismo , Corticosterona/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Factor de Transcripción Activador 6/metabolismo
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