Neural mechanisms underlying stress resilience in Ahi1 knockout mice: relevance to neuropsychiatric disorders
| Autor: | Tzuri Lifschytz, Esther Channah Broner, Hagit Cohen, Amit Lotan, G Goelman, B. Lerer, Y. Fellig, Lior Greenbaum, Alexandra Slonimsky, O Lory, S. Abedat |
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| Rok vydání: | 2013 |
| Předmět: |
Hypothalamo-Hypophyseal System
Elevated plus maze Rest Pituitary-Adrenal System Hippocampus Anxiety Environment Motor Activity Amygdala Body Temperature Mice Cellular and Molecular Neuroscience Proto-Oncogene Proteins medicine Animals Social Behavior Molecular Biology Mice Knockout Neurons Social stress Brain Sensory Gating Entorhinal cortex Mice Inbred C57BL Ventral tegmental area Adaptor Proteins Vesicular Transport Psychiatry and Mental health medicine.anatomical_structure Anxiogenic Knockout mouse Schizophrenia Corticosterone Psychology Neuroscience Stress Psychological |
| Zdroj: | Molecular Psychiatry. 19:243-252 |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/mp.2013.123 |
| Popis: | The Abelson helper integration site 1 (AHI1) gene has a pivotal role in brain development. Studies by our group and others have demonstrated association of AHI1 with schizophrenia and autism. To elucidate the mechanism whereby alteration in AHI1 expression may be implicated in the pathogenesis of neuropsychiatric disorders, we studied Ahi1 heterozygous knockout (Ahi1(+/-)) mice. Although their performance was not different from wild-type mice on tests that model classical schizophrenia-related endophenotypes, Ahi1(+/-) mice displayed an anxiolytic-like phenotype across different converging modalities. Using behavioral paradigms that involve exposure to environmental and social stress, significantly decreased anxiety was evident in the open field, elevated plus maze and dark-light box, as well as during social interaction in pairs. Assessment of core temperature and corticosterone secretion revealed a significantly blunted response of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis in Ahi1(+/-) mice exposed to environmental and visceral stress. However, response to centrally acting anxiogenic compounds was intact. On resting-state functional MRI, connectivity of the amygdala with other brain regions involved in processing of anxiogenic stimuli and inhibitory avoidance learning, such as the lateral entorhinal cortex, ventral hippocampus and ventral tegmental area, was significantly reduced in the mutant mice. Taken together, our data link Ahi1 under-expression with a defect in the process of threat detection. Alternatively, the results could be interpreted as representing an anxiety-related endophenotype, possibly granting the Ahi1(+/-) mouse relative resilience to various types of stress. The current knockout model highlights the contribution of translational approaches to understanding the genetic basis of emotional regulation and its associated neurocircuitry, with possible relevance to neuropsychiatric disorders. |
| Databáze: | OpenAIRE |
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