Senescence accelerated mouse strain is sensitive to neurodegeneration induced by mild impairment of oxidative metabolism.
Neuronal loss and impairment of oxidative metabolism are frequently observed in aging associated neurodegenerative diseases. Thiamine deficiency (TD) induces the region selective neuronal loss in the brain, which has been used to model neurodegeneration, accompanied by mild impairment of oxidative metabolism. C57BL/6 mice were commonly used animals for TD experiments; however, the individual variations among C57BL/6 mice in response to TD limited the consistence of brain pathology. The senescence accelerated prone 8 (SAMP8) mouse strain exhibits age-related morphological changes in the brain and deficits in learning and memory. In this study, we compared the effects of TD on SAMP8 mice, senescence accelerated resistant 1 (SAMR1) mice and C57BL/6 mice. TD-induced body weight loss in SAMP8 mice was much greater than in SAMR1 and C57BL/6 mice. In addition, earlier and more severe loss of neurons in the submedial thalamic nucleus (SmTN) of the thalamus was detected in the SAMP8 mice. After 8 days of TD (TD8), the loss of NeuN-positive neurons in the SmTN of SAMP8, SAMR1 and C57BL/6 mice was 65%, 50%, and 36%, respectively. TD also caused accumulation of amyloid precursor protein (APP) in the thalamus. After TD10, APP immunoreactivity in the thalamus of SAMP8 was much more intense than that of SAMR1 and C57BL/6 mice. These results suggest that SAMP8 mice are sensitive to TD and therefore offer a useful model for studying aging related neurodegeneration caused by the impairment of oxidative metabolism.
Zhang
Qipeng
Q
Institute of Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, PR China.
Ding
Hanqing
H
Li
Wenxia
W
Fan
Zhiqin
Z
Sun
Anyang
A
Luo
Jia
J
Ke
Zun-Ji
ZJ
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D004268:DNA-Binding Proteins; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress; D011726:Pyridinium Compounds; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology*; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D015431:Weight Loss / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D011726:Pyridinium Compounds