Effect of chronic unpredictable stress on mice with developmental under-expression of the Ahi1 gene: behavioral manifestations and neurobiological correlates

The Abelson helper integration site 1 (Ahi1) gene plays a pivotal role in brain development and is associated with genetic susceptibility to schizophrenia, and other neuropsychiatric disorders. Translational research in genetically modified mice may reveal the neurobiological mechanisms of such asso...

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Published in:Translational psychiatry 2018-07, Vol.8 (1), p.124-11, Article 124
Main Authors: Wolf, Gilly, Lifschytz, Tzuri, Ben-Ari, Hagar, Tatarskyy, Pavel, Merzel, Tirzah Kreisel, Lotan, Amit, Lerer, Bernard
Format: Article
Language:English
Subjects:
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Behavioral Sciences
Biological Psychology
Medicine
Medicine & Public Health
Neurobiology
Neurosciences
Pharmacotherapy
Psychiatry
Schizophrenia
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Summary:The Abelson helper integration site 1 (Ahi1) gene plays a pivotal role in brain development and is associated with genetic susceptibility to schizophrenia, and other neuropsychiatric disorders. Translational research in genetically modified mice may reveal the neurobiological mechanisms of such associations. Previous studies of mice heterozygous for Ahi1 knockout (Ahi1+/−) revealed an attenuated anxiety response on various relevant paradigms, in the context of a normal glucocorticoid response to caffeine and pentylenetetrazole. Resting-state fMRI showed decreased amygdalar connectivity with various limbic brain regions and altered network topology. However, it was not clear from previous studies whether stress-hyporesponsiveness reflected resilience or, conversely, a cognitive-emotional deficit. The present studies were designed to investigate the response of Ahi1+/− mice to chronic unpredictable stress (CUS) applied over 9 weeks. Wild type (Ahi1+/+) mice were significantly affected by CUS, manifesting decreased sucrose preference ( p  
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-018-0171-1