Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer's disease  

作　　者：Lihua Liu Saiping Luo Leping Zeng Weihong Wang Liming Yuan Xiaohong Jian 

机构地区：[1]Department of Histology & Embryology, School of Basic Medical Sciences, Central South University [2]Department of Nursing, Medical College of Hunan Normal University [3]Third Department of Surgery, Agricultural Division Four Hospital, Xinjiang Production and Construction Corps [4]Department of Anatomy & Neurobiology, School of Basic Medical Sciences, Central South University [5]Department of Anatomy, Medical College of Hunan Normal University

出　　处：《Neural Regeneration Research》2013年第24期2249-2255,共7页中国神经再生研究（英文版）

基　　金：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;a grant from the Scientific Research Program of Hunan Provincial Higher Education Institutes, No. 11C0829

摘　　要：Mice carrying mutant amyloid 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-13 protein 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 cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell 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.Mice carrying mutant amyloid 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-13 protein 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 cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell 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.

关 键 词：neural regeneration PRESENILIN-1 Alzheimer＇s disease tyrosine hydroxylase locus coeruleus noradrenergic neuron ^-amyloid senile plaques grants-supported paper NEUROREGENERATION 

分 类 号：R749.16[医药卫生—神经病学与精神病学]