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Reduced apurinic/apyrimidinic endonuclease 1 activity and increased DNA damage in mitochondria are related to enhanced apoptosis and inflammation in the brain of senescence- accelerated P8 mice (SAMP8)

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Torregrosa Muñumer, R. and Gómez, A. and Vara, E. and Kireev, R. and Barja de Quiroga Losada, Gustavo and Fernández Tresguerres Hernández, Jesús Ángel and Gredilla, R. (2016) Reduced apurinic/apyrimidinic endonuclease 1 activity and increased DNA damage in mitochondria are related to enhanced apoptosis and inflammation in the brain of senescence- accelerated P8 mice (SAMP8). Biogerontology, 17 (2). pp. 325-335. ISSN 1389-5729

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Official URL: https://link.springer.com/journal/10522



Abstract

The senescence- accelerated mouse prone 8 (SAMP8) is a well- characterized animal model of senescence that shows early age- related neurodegeneration with impairment in learning and memory skills when compared with control senescence- resistant mice (SAMR1). In the current study, we investigated whether such impairment could be partly due to changes in mitochondrial DNA (mtDNA) repair capacity and mitochondrial DNA damage in the brain of SAMP8 mice. Besides we studied whether these potential changes were related to modifications in two major processes likely involved in aging and neurodegeneration: apoptosis and inflammation. We observed that the specific activity of one of the main mtDNA repair enzymes, the mitochondrial APE1, showed an age- related reduction in SAMP8 animals, while in SAMR1 mice mitochondrial APE1 increased with age. The reduction in mtAPE1 activity in SAMP8 animals was associated with increased levels of the DNA oxidative damage marker 8oxodG in mtDNA. Our results also indicate that these changes were related to a premature increase in apoptotic events and inflammation in the brain of SAMP8 mice when compared to SAMR1 counterparts. We suggest that the premature neurodegenerative phenotype observed in SAMP8 animals might be due, at least in part, to changes in the processing of mtDNA oxidative damage, which would lead to enhancement of apoptotic and inflammatory processes.


Item Type:Article
Uncontrolled Keywords:SAMP8; Aging; Neurodegeneration; Mitochondrial DNA repair; 8-Hydroxydeoxyguanosine; Apoptosis; Inflammation
Subjects:Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Mammals
ID Code:42697
Deposited On:11 May 2017 14:21
Last Modified:12 May 2017 08:41

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