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-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 situ and Northern blot hybridization confirmed the expression of huntingtin 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 huntingtin 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.
Hebb
M O
MO
Laboratory of Molecular Neurobiology, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
Denovan-Wright
E M
EM
Robertson
H A
HA
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000302:isolation & purification; D000071058:Huntingtin Protein; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009490:Neurosecretory Systems / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D015345:Oligonucleotide Probes; D049590:Postpartum Period / Q000378:metabolism*; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D005904:Glial Fibrillary Acidic Protein; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger