@PHDTHESIS{ 2020:1021682437,
 	title = {Effect of lipoic acid supplementation on cognitive deficits, genomic stability and mitochondrial damage in the hippocampus of wistar rats submitted to iron overload in the neonatal period},
 	year = {2020},
 	url = "http://tede2.pucrs.br/tede2/handle/tede/9310",
 	abstract = "Aging is a multifactorial process that leads to a series of organic alterations, affecting multiple systems, including the nervous system. Thus, aging has been considered the main risk factor for the progression of neurodegeneration, which has also been associated with increased DNA damage, mitochondrial decline, as well as cognitive dysfunction. . Moreover, age-related iron accumulation in the nervous system can also be viewed as an important contributing factor for neurodegeneration, since iron excess may lead to oxidative and mitochondrial damage and changes in learning and memory. There is evidence that mitochondrial antioxidants could act to reduce oxidative stress and improve mitochondrial function in the nervous system and consequently present a positive effect on cognitive aspects. It has been reported that Lipoic acid (LA), a natural antioxidant, and essential cofactor in mitochondria, prevents oxidative damage and improves antioxidants defences associated with aging and improves cognitive functions. The aim of the present study was to investigate the effects of LA supplementation during adulthood combined with supplementation later in life or administered at old age only, on cognitive parameters, mitochondrial DNA (mtDNA) damage and antioxidant responses of aged rats submitted to neonatal iron overload. Furthermore, to review the current literature on the use and biological effects of LA in the central nervous system functioning, as well to give support for its use as a potential coadjuvant in the treatment of memory dysfunctions associated to neurodegenerative disorders. Our results showed that aged rats presented long-term recognition memory impairments and that iron overload also impairs aversive memory in aged rats. Combined LA treatment was able to reverse recognition and aversive memory impairments induced by iron in aged rats, while LA treatment at old age only reversed iron-induced aversive memory impairments. Neither iron nor LA treatments altered general exploratory behavioral parameters analysed in the open field, suggesting that the effects described here are related to the cognitive aspects of behaviour. Molecular analysis showed that iron overload in the neonatal period induced higher mtDNA deletions in the hippocampus of aged rats, suggesting that iron overload may contribute to mitochondrial dysfunctions. LA treatment was able to reverse ironinduced increases in mtDNA deletions and the combined treatment was more effective than LA given at old age only. Nonetheless, we also demonstrated that iron overload induces the apoptotic pathway in the hippocampus of aged rats, since caspase 3 expression was increased, and LA was able to reverse iron-induced caspase 3 increases, suggesting that LA presents antiapoptotic effects. In present study, iron overload in neonatal period also increased the expression of Nrf2 in the hippocampus of aged rats, which might be attributed to over generation of oxidative stress. LA supplementation, partially reversed iron effects in inducing Nrf2 expression when given in the old age only, however, LA supplementation in adulthood and later in life lead to a complete reversion of iron-induced effects on Nrf2 expression thus protecting the hippocampus against iron-induced neurotoxicity. Additionally, Gpx1, Nqo1, and CAT expression accompanied increased Nfr2 expression, suggesting that iron exposure in the neonatal period resulted in increased oxidant state in aged rats, which was normalized by LA treatment. Thus, the findings of the present study confirmed the evidences reported in the literature review suggesting a neuroprotector effect of LA, and showed that LA supplementation may protect against cognitive decline, mitochondrial damage and antioxidant imbalance related to aging and neurodegenerative disorders.",
 	publisher = {Pontif?cia Universidade Cat?lica do Rio Grande do Sul},
 	scholl = {Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de},
 	note = {Escola de Medicina}
}