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

被引:33
作者
Hebb, MO [1 ]
Denovan-Wright, EM [1 ]
Robertson, HA [1 ]
机构
[1] Dalhousie Univ, Dept Pharmacol, Mol Neurobiol Lab, Halifax, NS B3H 4H7, Canada
关键词
glia; lactation; Sprague-Dawley; epidermal growth factor receptor;
D O I
10.1096/fasebj.13.9.1099
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-type or mutated form of huntingtin is currently unknown. We have observed that relative to naive and male animals, huntingtin protein was significantly increased in the arcuate nucleus of postpartum rats. Using an oligonucleotide 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 expression of huntingtin mRNA in postpartum, lactating animals compared with naive female or male animals. Emulsion autoradiography and immunohistochemistry revealed that the cells with elevated huntingtin expression had a stellate conformation that morphologically resembled astrocytes. Dual label immunofluorescence immunohistochemistry demonstrated the colocalization of huntingin and glial fibrillary acidic protein in these cells, confirming that they were astrocytes, Astrocytes expressing huntingtin were consistently found in close apposition to neuronal soma, suggesting interactions between these cell types. During the perinatal and postnatal period, the hypothalamus undergoes 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 function.
引用
收藏
页码:1099 / 1106
页数:8
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