Inosine improves cognitive function and decreases aging-induced oxidative stress and neuroinflammation in aged female rats

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Abstract

In the present study, the effect of inosine was evaluated on learning and memory of 18 months old aged female rats. Inosine (50, 100 and 200 mg/kg; i.p.) was administered to separate groups of rats for 15 successive days. Donepezil (1 mg/kg; i.p.), an acetylcholinesterase inhibitor, was used as a standard drug. Behavioral models such as Morris water maze and elevated plus maze were used to evaluate the effect of drugs on learning and memory of rats. After behavioral studies, animals were killed and their brain was isolated and further processed for estimation of various biochemical parameters such as acetylcholinesterase activity, oxidative stress markers, proinflammatory marker and histological examinations. Inosine (100 and 200 mg/kg) significantly improved learning and memory of aged rats. Further, inosine significantly reduced lipid peroxidation and nitrite, and increased the levels of reduced glutathione and superoxide dismutase. However, no significant difference in AChEs activity was observed in inosine-treated rats as compared to aged control rats. TNF-α level was found to be ameliorated in aged rats by inosine. Histopathological evaluation showed that inosine-treated aged rats have less number of pyknotic neurons in hippocampal CA1 region as compared to aged control rats. In conclusion, inosine significantly improved learning and memory of aged female rats possibly through its antioxidant as well as anti-inflammatory effect and improvement of neuronal survival in the hippocampal CA1 region. However, additional studies are required to further explore the downstream signaling pathways involved in the neuroprotective effect of inosine in aged animals.

Keywords

Aging Dementia Inosine Learning Memory 

Abbreviations

AChE

Acetylcholinesterase

AD

Alzheimer’s disease

ANOVA

Analysis of variance

CPCSEA

Committee for the Purpose of Control and Supervision of Experiments on Animals

DTNB

5,5′ dithio-bis-2-nitro benzoic acid

EL

Escape latency

GSH

Reduced glutathione

ITL

Initial transfer latency

LPO

Lipid peroxidation

MDA

Malondialdehyde

NO

Nitric oxide

RTL

Retention transfer latency

SOD

Superoxide dismutase

TL

Transfer latency

TSTQ

Time spent in target quadrant

WHO

World Health Organization

Notes

Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors would like to thank the Honorable Vice-Chancellor, Guru Jambheshwar University of Science and Technology for providing financial support and infrastructural facilities to carry out this work.

Authors contributions

DD conceptualized the project; PR planned and performed the experiments (animal behavioral study, biochemical estimations, ELISAs, histology); DD and PR analyzed all the data and wrote the manuscript. Authors critically reviewed the manuscript and approved for final submission.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest among authors.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pharmacology Division, Department of Pharmaceutical SciencesGuru Jambheshwar University of Science and TechnologyHisarIndia

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