Expression of the Huntington's disease gene is regulated in astrocytes in the arcuate nucleus of the hypothalamus of postpartum rats

Huntington's disease (HD) is one of a number of neurodegenerative disorders caused by expansion of polyglutamine-encoding CAG repeats within specific genes. Huntingtin, the protein product of the HD gene, is widely expressed in neural and nonneural human and rodent tissue. The function of the wild-t ype or mutated form of huntingtin is currently unknown. We have observed th at relative to naive and male animals, huntingtin protein was significantly increased in the arcuate nucleus of postpartum rats. Using an oligonucleot ide probe, in sih and Northern blot hybridization confirmed the expression of hunting-tin mRNA, Quantification of the in situ hybridization signal in the arcuate nucleus revealed an approximate sevenfold increase in the expre ssion of huntingtin mRNA in postpartum, lactating animals compared with nai ve female or male animals. Emulsion autoradiography and immunohistochemistr y revealed that the cells with elevated huntingtin expression had a stellat e conformation that morphologically resembled astrocytes. Dual label immuno fluorescence immunohistochemistry demonstrated the colocalization of huntin gin and glial fibrillary acidic protein in these cells, confirming that the y were astrocytes, Astrocytes expressing huntingtin were consistently found in close apposition to neuronal soma, suggesting interactions between thes e cell types. During the perinatal and postnatal period, the hypothalamus u ndergoes alterations in metabolic function. Our results support the idea of glia-induced metabolic changes in the hypothalamus, These results provide the first demonstration of naturally occurring changes in the expression of the Huntington's disease gene in the brain and suggest that huntingtin may play an important role in the processes that regulate neuroendocrine funct ion.