Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer’s disease****
Lihua Liu
Saiping Luo
Leping Zeng
Weihong Wang
Liming Yuan
Xiaohong Jian
摘要： Mice carrying mutant amyloid-β precursor protein and presenilin-1 genes (APP/PS1 double trans-genic mice) have frequently been used in studies of Alzheimer’s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer’s disease is known to correlate with the amount of amyloid-βprotein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age: young mice (5–6 months old) and aged mice (16–17 months old). Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase (a marker of catecholaminergic neurons in the locus coeruleus) revealed that APP/PS1 mice had 23%fewer cel s in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cel bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy-droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.
机标关键词：tyrosine hydroxylaselocus coeruleustransgenic micecatecholaminergic neuronsused in
资助基金：This study was supported by the National Natural Science Foundation of China, (No.81100663)the Scientific Research Funds of the Health Department of Hunan Province, (No.120303)Hunan Provincal Natural Science Foundation of China, (No.13JJ3058 and a grant from the Scientific Research Program of Hunan Provincial Higher Education Institutes, No.11C0829)
论文发表日期：2013-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 2249-2255 )
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