科研之友
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摘要
In Huntington disease (HD), hypothalamic neuropeptidergic systems are not equally affected at the peptide and mRNA levels. Because prohormone convertases (PCs) are critically involved in the conversion of propeptides into their active forms, we postulated that a decrease in PC expression may underlie these discrepancies. Therefore, we assessed the expression of PC1/3 and PC2 in the hypothalamic infundibular, suprachiasmatic, and paraventricular nuclei in postmortem tissues of HD patients and controls (n = 9, each) using immunocytochemistry and quantitative reverse transcription polymerase chain reaction. We also assessed PC1/3 and PC2 mRNA expression in the inferior frontal gyrus and colocalization of both PCs with corticotropin-releasing hormone and alpha-melanocyte-stimulating hormone. In HD patients, PC1/3 and PC2 expression was decreased in the hypothalamic infundibular (both p = 0.046) and paraventricular nuclei (p = 0.031 and p = 0.019). In the suprachiasmatic nucleus, PC1/3 and PC2 expressions were not different between HD and control cases; PC1/3 and PC2 mRNA levels in the inferior frontal gyrus were also not different. None of the PCs was colocalized with corticotropin-releasing hormone, whereas alpha-melanocyte-stimulating hormone showed colocalization with PC1/3 and PC2. These data suggest that defects in the processing of hypothalamic neuropeptides in HD may partially arise from decreased PC1/3 and PC2 expressions. These changes might contribute to selective neuropathology underlying various clinical manifestations and may provide novel therapeutic targets in HD patients.
- 出版日期2013-12
