Effects of Deletion of Mutant Huntingtin in Steroidogenic Factor 1 Neurons on the Psychiatric and Metabolic Phenotype in the BACHD Mouse Model of Huntington Disease

摘要: Psychiatric and metabolic features appear several years before motor disturbances in the neurodegenerative Huntington’s disease (HD), caused by an expanded CAG repeat huntingtin (HTT) gene. Although mechanisms leading to these aspects are unknown, dysfunction hypothalamus, a brain region controlling emotion metabolism, has been suggested. A direct link between expression of causing protein, (HTT), hypothalamus development psychiatric-like have shown BACHD mouse model HD. However, precisely which circuitry is critical for not known. We hypothesized that mutant HTT ventromedial area involved regulation metabolism would be important non-motor aspects. Therefore, we inactivated specific neuronal population expressing transcription factor steroidogenic 1 (SF1) using cross-breeding based on Cre-loxP system. Effects anxiety-like behavior were assessed elevated plus maze novelty-induced suppressed feeding test. Depressive-like was Porsolt forced swim phenotype analyzed measurements body weight fat, as well serum insulin leptin levels. Interestingly, inactivation SF1-expressing neurons exerted partial positive effect depressive-like female mice at 4 months age. In this cohort mice, no detected. The deletion SF1 did any mice. Taken together, our results indicate regulates networks affecting hypothalamic circuitries do involve hypothalamus.