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ATF6β Deficiency Elicits Anxiety-like Behavior and Hyperactivity Under Stress Conditions.

Authors :
Tanaka, Takashi
Nguyen, Dinh Thi
Kwankaew, Nichakarn
Sumizono, Megumi
Shinoda, Reika
Ishii, Hiroshi
Takarada-Iemata, Mika
Hattori, Tsuyoshi
Oyadomari, Seiichi
Kato, Nobuo
Mori, Kazutoshi
Hori, Osamu
Source :
Neurochemical Research. Jul2023, Vol. 48 Issue 7, p2175-2186. 12p.
Publication Year :
2023

Abstract

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 ATF6β, 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 ATF6β 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 ATF6β deficiency produces anxiety-like behavior and hyperactivity via a CRH receptor 1-dependent mechanism. ATF6β could play a role in psychiatric conditions in the emotional centers of the brain. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03643190
Volume :
48
Issue :
7
Database :
Academic Search Index
Journal :
Neurochemical Research
Publication Type :
Academic Journal
Accession number :
163721717
Full Text :
https://doi.org/10.1007/s11064-023-03900-4