Mitochondrial DNA deletions parallel age-linked decline in rat sensory nerve function

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• 作者：Nagley ; Phillip ; Zhang ; Chunfang ; Lim ; Maria L.R. ; Merhi ; Merhi ; Needham ; B. Elise ; Khalil ; Zeinab
• 关键词：Mitochondrial DNA ; Multiple deletions ; Dorsal root ganglia ; Capsaicin ; Animal model ; Polymerase chain reaction ; Vascular response ; Substance P ; Sciatic nerve ; Rat
• 刊名：Neurobiology of Aging
• 出版年：2001
• 出版时间：July - August, 2001
• 年：2001
• 卷：22
• 期：4
• 页码：635-643
• 全文大小：268 K

文摘

In rats, the function of sensory nerves in the hind limb declines significantly with age. Normally aging rats and rats treated neonatally with capsaicin were studied here. Quantification of vascular response and substance P in young (3 months) and old (24 months) rats showed additive effects of age and capsaicin treatment. The levels in dorsal root ganglion of a particular deletion in mitochondrial DNA (mtDNA⁴⁸³⁴) were about 300-fold higher in old compared to young rats. Capsaicin treatment had no significant effect on mtDNA⁴⁸³⁴ abundance. Dorsal root ganglia of old (but not young) rats were found to contain a spectrum of multiple deletions. The abundance of mtDNA⁴⁸³⁴ in dorsal root ganglia from individual rats correlated strongly with their decline in vascular function, even where vascular responses were systematically depressed due to prior capsaicin treatment. One possibility is that mitochondrial DNA mutations directly lead to functional decline at mitochondrial and tissue levels. Alternatively, loss of mitochondrial DNA integrity and physiological decline may be consequences of the same factor, such as oxidative stress.