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Rejuvenation Res. 2018 Aug 23. doi: 10.1089/rej.2018.2070. [Epub ahead of print]

Rapamycin Confers Neuroprotection Against Aging-Induced Oxidative Stress, Mitochondrial Dysfunction, and Neurodegeneration in Old Rats Through Activation of Autophagy.

Author information

1
1 Department of Biochemistry, University of Allahabad , Allahabad, India .
2
2 Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh , Noida, India .
3
3 Department of Animal Science and Biotechnology, Chonbuk National University , Jeonju, Republic of Korea.
4
4 Department of Biomedical Engineering, National Institute of Technology , Raipur, India .

Abstract

Brain aging is an intricate and natural phenomenon exclusively characterized by oxidative stress, accumulation of oxidatively damaged macromolecules, and alterations in structure and function of neurons that further increase the risk factor for most of the neurodegenerative diseases. In addition, age-dependent defective autophagy has also been implicated to favor the pathogenesis and prevalence of the neurological diseases. Therefore, the development of strategies that delay aging and the concomitant neurological disorders remain elusive. Thus, the present study was undertaken to investigate the effect of rapamycin-induced activation of autophagy on aging-related oxidative stress, cell death, neuroinflammation, and neurodegeneration in rat brain. Our data demonstrated the significant age-related oxidative stress, apoptotic cell death, elevated inflammatory response, and reduced level of markers associated with rejuvenation and neural integrity, including the activities of ion channel transporters (Na+/K+-ATPase and Ca2+-ATPase) and acetylcholinesterase in the brain of old aged rats. Furthermore, rapamycin (0.5 mg/kg b.w. for 28 days) induced activation of autophagy provided significant protection to aging rat brain by reducing the aging-induced oxidative stress, apoptotic cell death, and markers of neurodegeneration. Thus, our data confirmed that autophagy plays a pivotal role in delaying brain aging plausibly by maintaining the cellular homeostasis, and structural and functional integrity of cells in the brain.

KEYWORDS:

aging; autophagy; neuroinflammation; neuroprotection; oxidative stress; rapamycin

PMID:
29943667
DOI:
10.1089/rej.2018.2070

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