Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice

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Although the majority of the neurons in the brain are generated during embryonic stage, new neurons are continuously being produced postnatally, and at a much lower rate in adulthood. As postnatal neurogenesis is a key component of the brain maturation process that creates dynamic ‘wirings’ in the brain necessary for an individual to grow, learn, and cope with the external world, attenuated postnatal neurogenesis may affect an individual’s mental stability, rendering a higher susceptibility to depression later in life. In the current study, we genetically ablated the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions, and found that early loss of Hap1 significantly reduces postnatal hippocampal neurogenesis, and leads to adult depressive-like behavior. We also found c-kit as an effector to mediate the neurogenesis defect and adult depressive-like phenotype in mice lacking Hap1. The results provide the first genetic evidence to demonstrate the importance of postnatal neurogenesis in adult depression, and may offer new avenues in the prevention and treatment of depression. Our study also has potential implications to other adult-onset mental disorders.

Vyšlo v časopise: Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005175
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005175

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