title: Aging modifies daily variation of antioxidant enzymes and oxidative status in the hippocampus.
abstract: Aging is a complex and multifactorial biological process that leads to the progressive deterioration of physiological systems, including the circadian system. In addition, oxidative stress has been associated with the aging of the normal brain and the development of late-onset neurodegenerative diseases. Even though, functional weakening of circadian rhythms and antioxidant function has been observed during aging, the mechanisms by which the circadian system signaling and oxidative stress are interrelated have not yet been elucidated. The objectives of this study were to evaluate the consequences of aging on the temporal organization of the antioxidant defense system and oxidative status as well as to analyze the endogenous clock activity, in the hippocampus of aged rats.
  
  
  
  Young adults (3-month-old) or older (22-month-old) male Holtzman rats were maintained under constant darkness conditions, during 15days before the sacrifice. Levels of catalase (CAT) and glutathione peroxidase (GPx) mRNA and activity, reduced glutathione (GSH), lipoperoxidation (LPO) and BMAL1 protein were analyzed in hippocampus samples isolated every 4h during a 24-h period. Locomotor activity was recorded during 20days before the experiment.
  
  
  
  Our results show that aging modifies temporal patterns of CAT and GPx expression and activity in the hippocampus in a different way. On the one hand, it abolishes the oscillating CAT expression and specific enzymatic activity while, on the other, it increases the mesor of circadian GPx activity rhythm (p<0.01). Additionally, we observed increased GSH (p<0.05) and reduced LPO (p<0.01) levels in the hippocampus of aged rats. Moreover, the nocturnal locomotor activity was reduced in the older animals in comparison to the young adult rats (p<0.01). Interestingly, the 22month-old animals became arrhythmic and showed a marked fragmentation as well as a significant decline in daily locomotor activity when they were maintained under constant darkness conditions (p<0.05). Aging also abolished circadian rhythms of the core clock BMAL1 protein.
  
  
  
  The loss of temporal organization of the antioxidant enzymes activity, the oxidative status and the cellular clock machinery could result in a temporally altered antioxidant defense system in the aging brain. Learning about how aging affects the circadian system and the expression of genes involved in the antioxidant defense system could contribute to the design of new strategies to improve the quality of life of older people and also to promote a healthy aging.
authors.affiliation: Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research - San Luis (IMIBIO-SL), National Council for Science and Technology (CONICET), National University of San Luis (UNSL), Ejército de los Andes 950, D5700HHW San Luis, Argentina. Electronic address: gabnela@unsl.edu.ar.
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Lacoste
authors.affiliation: Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research - San Luis (IMIBIO-SL), National Council for Science and Technology (CONICET), National University of San Luis (UNSL), Ejército de los Andes 950, D5700HHW San Luis, Argentina.
authors.forename: Ivana Tamara
authors.initials: IT
authors.lastname: Ponce
authors.affiliation: Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research - San Luis (IMIBIO-SL), National Council for Science and Technology (CONICET), National University of San Luis (UNSL), Ejército de los Andes 950, D5700HHW San Luis, Argentina.
authors.forename: Rebeca Laura
authors.initials: RL
authors.lastname: Golini
authors.affiliation: Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research - San Luis (IMIBIO-SL), National Council for Science and Technology (CONICET), National University of San Luis (UNSL), Ejército de los Andes 950, D5700HHW San Luis, Argentina; Laboratory of Biology Reproduction, Multidisciplinary Institute of Biological Research-San Luis (IMIBIO-SL), National Council of Science and Technology (CONICET), National University of San Luis (UNSL), Ejército de los Andes 950, D5700HHW San Luis, Argentina.
authors.forename: Silvia Marcela
authors.initials: SM
authors.lastname: Delgado
authors.affiliation: Laboratory of Chronobiology, Multidisciplinary Institute of Biological Research - San Luis (IMIBIO-SL), National Council for Science and Technology (CONICET), National University of San Luis (UNSL), Ejército de los Andes 950, D5700HHW San Luis, Argentina.
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Anzulovich
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione
keywords: Aging; Antioxidant enzyme; Circadian rhythm; Hippocampus; Oxidative status