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Decreased expression of hypothalamic neuropeptides in Huntington disease transgenic mice with expanded polyglutamine‐EGFP fluorescent aggregates
Author(s) -
Kotliarova Svetlana,
Jaihar R.,
Sakamoto Naoaki,
Kurosawa Masaru,
Miyazaki Haruko,
Nekooki Munenori,
Doi Hiroshi,
Machida Yoko,
Wong Hon Kit,
Suzuki Taishi,
Uchikawa Chiharu,
Kotliarov Yuri,
Uchida Kazuyo,
Nagao Yoshiro,
Nagaoka Utako,
Tamaoka Akira,
Oyanagi Kiyomitsu,
Oyama Fumitaka,
Nukiobuyuki
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03035.x
Subject(s) - huntingtin , striatum , green fluorescent protein , neuropeptide , biology , huntington's disease , transgene , hypothalamus , genetically modified mouse , cerebrum , microbiology and biotechnology , in situ hybridization , cerebral cortex , messenger rna , endocrinology , medicine , mutant , central nervous system , gene , biochemistry , receptor , disease , dopamine
Huntington disease is caused by polyglutamine (polyQ) expansion in huntingtin. Selective and progressive neuronal loss is observed in the striatum and cerebral cortex in Huntington disease. We have addressed whether expanded polyQ aggregates appear in regions of the brain apart from the striatum and cortex and whether there is a correlation between expanded polyQ aggregate formation and dysregulated transcription. We generated transgenic mouse lines expressing mutant truncated N‐terminal huntingtin (expanded polyQ) fused with enhanced green fluorescent protein (EGFP) and carried out a high‐density oligonucleotide array analysis using mRNA extracted from the cerebrum, followed by TaqMan RT‐PCR and in situ hybridization. The transgenic mice formed expanded polyQ‐EGFP fluorescent aggregates and this system allowed us to directly visualize expanded polyQ aggregates in various regions of the brain without performing immunohistochemical studies. We show here that polyQ‐EGFP aggregates were intense in the hypothalamus, where the expression of six hypothalamic neuropeptide mRNAs, such as oxytocin, vasopressin and cocaine‐amphetamine‐regulated transcript, was down‐regulated in the transgenic mouse brain without observing a significant loss of hypothalamic neurons. These results indicate that the hypothalamus is susceptible to aggregate formation in these mice and this may result in the down‐regulation of specific genes in this region of the brain.