Association of exercise-induced autophagy upregulation and apoptosis suppression with neuroprotection against pharmacologically induced Parkinson's disease

Abstract

[Purpose]We investigated whether treadmill exercise (TE)-induced neuroprotection was associated with enhanced autophagy and reduced apoptosis in a mouse model of pharmacologically induced Parkinson's disease (PD).[Methods]PD was induced via the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 male mice were randomly assigned to the following three groups: control (C57BL, n=10), MPTP with probenecid (MPTP/C, n=10), and MPTP/ C plus exercise (MPTP-TE, n=10). The MPTP-TE mice performed TE training (10 m/min, 60 min/day, 5 days/week) for 8 weeks. The rotarod test was used to assess motor function.[Results]TE restored MPTP/P-induced motor dysfunctionand increased tyrosine hydroxylase levels. Furthermore, TE diminished the levels of α-synuclein (α-syn), a neurotoxin; modulated the levels of autophagy-associated proteins, including microtubule-associated protein 1 light chain 3-II, p62, BECLIN1, BNIP3, and lysosomal-associated membrane protein-2, which enhanced autophagy; inhibited the activation of proapoptotic proteins (caspase-3 and BAX);and upregulated BCL-2, an antiapoptosis protein.[Conclusion]Taken together, these results suggested that the TE-induced neuroprotection against MPTP-induced cell death was associated with enhanced autophagy and neuronal regeneration based on the findings of inhibited proapoptotic events in the brains of the TE-trained animals.

What and How Can Physical Activity Prevention Function on Parkinson’s Disease?

“…Those factors were all downregulated in the PD mice group while reversed in the exercise group. Therefore, physical exercise relieve PD symptoms in multiple ways, such as the autophagic ability promotion of the cells [183] and mitochondrial function enhancement.…”

Effects of Physical Exercise on Autophagy and Apoptosis in Aged Brain: Human and Animal Studies

“…It has been postulated that regular physical exercise can promote a beneficial effect on the health of individuals and is considered an important autophagic inducer ( 180 – 183 ). It was observed that treadmill exercise (8 weeks) in mice modulated the levels of autophagy-associated proteins, including Beclin1, and improved autophagy ( 184 ). Based on literature data, it is suggested that physical exercise can induce autophagy through the following mechanism: exercise induces decreased adenosine triphosphate/adenosine monophosphate (ATP/AMP) in the cell, and this induces AMP-activated protein kinase (AMPK) activation; AMPK activation promotes inhibition of mammalian target of rapamycin (mTOR), leading to Unc-51 kinase 1 (ULK1) disinhibition, which is also phosphorylated and activated by AMPK; the ULK1 complex induces activation of the Phosphatidylinositol 3-kinase (PI3K) complex culminating in increased expression of autophagy-related proteins (Atgs); AMPK also promotes activation of autophagy-related transcription factors such as forkhead box O (FOXO), thereby increasing the expression of LC3-II and Atgs [for more detailed information on these signaling pathways, see ( 172 , 185 , 186 ) ( Figure 3B )].…”

Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?

“…Additionally, PA can take part in brain functions by improving mood, mental health, and cognitive activity by immune system-mediated effects [ 8 ]. Additionally, regular and moderate physical activity maintains the activation of glial cells within a healthy range, which may reduce or delay the progression of brain neurodegeneration [ 9 – 14 ].…”