Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.
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 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days 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.
Programa de Pós-Graduação em Ciências Biológicas: Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Gisele Agustini
GA
Lovatel
Viviane Rostirola
VR
Elsner
Karine
K
Bertoldi
Cláudia
C
Vanzella
Felipe Dos Santos
Fdos S
Moysés
Adriana
A
Vizuete
Christiano
C
Spindler
Laura Reck
LR
Cechinel
Carlos Alexandre
CA
Netto
Alysson Renato
AR
Muotri
Ionara Rodrigues
IR
Siqueira
D000107:Acetylation; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006657:Histones; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4