Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus

• Published in: Neurobiology of learning and memory Vol. 101; pp. 94 - 102
• Main Authors: Lovatel, Gisele Agustini, Elsner, Viviane Rostirola, Bertoldi, Karine, Vanzella, Cláudia, Moysés, Felipe dos Santos, Vizuete, Adriana, Spindler, Christiano, Cechinel, Laura Reck, Netto, Carlos Alexandre, Muotri, Alysson Renato, Siqueira, Ionara Rodrigues
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-03-2013; Elsevier; Elsevier BV
• Subjects: Acetylation; Aging; Aging - metabolism; Aging - physiology; Animals; Avoidance Learning - physiology; Behavioral psychophysiology; Biological and medical sciences; Cytokines; Epigenesis, Genetic; Epigenetics; Exercise; Forced exercise; Fundamental and applied biological sciences. Psychology; Hippocampus - metabolism; Histones - metabolism; Inflammation Mediators - metabolism; Interleukin-1beta - metabolism; Interleukin-1β; Interleukin-4; Interleukin-4 - metabolism; Male; Memory - physiology; Neurobiology; NF-kappa B - metabolism; Nuclear factor-kappaB; Physical Conditioning, Animal - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rat hippocampus; Rats; Rats, Wistar; Rodents; Treadmill; Tumor Necrosis Factor-alpha - metabolism; Tumor-necrosis factor alpha; Forced exercise; Interleukin-4; Interleukin-1β; Aging; Nuclear factor-kappaB; Treadmill; Rat hippocampus; Tumor-necrosis factor alpha; Physical exercise; Senescence; Rat; Memory; Central nervous system; Encephalon; Interleukin 4; Age; Tumor necrosis factor α; Treadmill exercise; Cytokine; Rodentia; Interleukin 1β; Vertebrata; Mammalia; Animal; Epigenesis; Hippocampus
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2013.01.007

• Aged rats hippocampi have an imbalance on inflammatory and histone acetylation status. • Forced exercise increases anti-inflammatory cytokine content in young hippocampus. • Exercise improves aversive memory and reverses the aging-induced H4 hipoacetylation. • Exercise was able to reverse the pro-inflammatory state induced by aging.
It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20min for 2weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18h, 3days or 7days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-β and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.