Regular and moderate exercise initiated in middle age prevents age-related amyloidogenesis and preserves synaptic and neuroprotective signaling in mouse brain cortex.
Although the beneficial responses induced in the central nervous system by early-initiated exercise have been broadly investigated, the effects of a chronic and moderate lately-initiated exercise on biochemical hallmarks of very early brain senescence have not been extensively studied. We previously reported that a midlife-initiated regimen of moderate running was able not only to prevent the age-related decay of antioxidative and detoxification functions in mouse brain cortex, but also to preserve neurotrophic support and molecular integrity. On this basis, this work investigated whether and how a 2-mo or 4-mo midlife-initiated running protocol could affect the activity of those systems involved in maintaining neuronal function and in preventing the onset of neurodegeneration within the brain cortex of middle-aged CD-1 mice. In particular, we analyzed the production of the peptide amyloid-β and the expression of synapsin Ia, which is known to play a key role in neurotransmission and synaptic plasticity. In addition, we studied the expression of sirtuin 3, as a protein marker of neuroprotection against age-dependent mitochondrial dysfunction, as well as the pro-death pathway induced by proBDNF through the interaction with p75NTR and the co-receptor sortilin. The midlife-initiated 4-mo running program triggered multiple responses within the mouse brain cortex, through the activation of anti-amyloidogenic, pro-survival, synaptogenic and neuroprotective pathways. However, most of the beneficial actions of the exercise regimen appeared only after 4months, since 2-mo-exercised mice showed marked impairments of the endpoints we considered. This could imply that a midlife-initiated regimen of moderate treadmill running may require an adequate time lag to activate beneficial compensative mechanisms within the mouse brain cortex.
Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Giosuè Carducci, 32 - Rotilio Center, L'Aquila (AQ), Italy.
Silvia
S
Di Loreto
Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito, L'Aquila (AQ), Italy. Electronic address: stefano.falone@univaq.it.
Stefano
S
Falone
Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito, L'Aquila (AQ), Italy.
Antonella
A
D'Alessandro
Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito, L'Aquila (AQ), Italy.
Silvano
S
Santini
Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Giosuè Carducci, 32 - Rotilio Center, L'Aquila (AQ), Italy.
Pierluigi
P
Sebastiani
Dept. of Biomedical Sciences, University "G. d'Annunzio", Via dei Vestini, Chieti Scalo (CH), Italy.
Marisa
M
Cacchio
Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Giosuè Carducci, 32 - Rotilio Center, L'Aquila (AQ), Italy; Dept. of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito, L'Aquila (AQ), Italy.
Fernanda
F
Amicarelli
D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D056566:Sirtuin 3 / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C525046:Sirt3 protein, mouse; D016704:Synapsins; D020932:Nerve Growth Factor; D056566:Sirtuin 3
Amyloid beta; Brain cortex; Exercise; Middle age; Neuroprotection; Sirtuins