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

摘要: The Abelson helper integration site 1 (Ahi1) gene plays a pivotal role in brain development and is associated with genetic susceptibility to schizophrenia, other neuropsychiatric disorders. Translational research genetically modified mice may reveal the neurobiological mechanisms of such associations. Previous studies heterozygous for Ahi1 knockout (Ahi1+/−) revealed an attenuated anxiety response on various relevant paradigms, context normal glucocorticoid caffeine pentylenetetrazole. Resting-state fMRI showed decreased amygdalar connectivity limbic regions altered network topology. However, it was not clear from previous whether stress-hyporesponsiveness reflected resilience or, conversely, cognitive-emotional deficit. present were designed investigate Ahi1+/− chronic unpredictable stress (CUS) applied over 9 weeks. Wild type (Ahi1+/+) significantly affected by CUS, manifesting sucrose preference (p < 0.05); reduced elevated plus maze light dark box thigmotaxis open field (p < 0.01 0.05); hyperthermic acute contextual fear conditioning (p < 0.01) increased neurogenesis (p < 0.05). In contrast, indifferent effects CUS assessed same parameters. Our findings suggest that under-expression during neurodevelopment, as manifested mice, renders these hyporesponsive. deficiency attenuate perception and/or environmental stressors result impaired corticolimbic or aberrant functional wiring. These neural provide initial clues schizophrenia