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Mefenamic Acid Attenuates Chronic Alcohol Induced Cognitive Impairment in Zebrafish: Possible Role of Cholinergic Pathway

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Abstract

Based on the scientific evidence supporting the neuroinflammatory response contributes the cognitive impairment associated with chronic alcoholism and the neuroprotective actions of mefenamic acid with reversal of memory loss and brain inflammation in mice, this study was designed to evaluate the effect of mefenamic acid against chronic alcohol induced cognitive impairment in zebrafish model. Zebrafish were grouped and subjected to normal behavioral analysis in light–dark chamber for 10 days. The preference to dark compartment was noted in zebrafish. Zebrafish were grouped and exposed to escalating doses of alcohol for 28 days with and without mefenamic acid exposure (100 and 200 µg/L) and subjected to a fear conditioning passive avoidance task from day 13 of 28. The cognitive evaluation was performed for 10 days and the brain tissue was isolated to estimate acetylcholinesterase activity. In cognitive evaluation study, the normal zebrafish retained the memory of the learned task and avoided the dark. The alcohol exposed zebrafish showed impairment in retaining the memory of learned task. Mefenamic acid exposed zebrafish showed a significant protection against cognitive impairment caused by alcohol and retained the memory of learned task with a significant decrease in AChE activity in brain homogenate compared to alcohol exposed zebrafish. The results of this study suggest that the memory enhancing activity of mefenamic acid might be due to activation of cholinergic transmission that has protected neuroinflammatory and neurodegenerative conditions caused by alcohol.

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Acknowledgements

The authors are thankful to the management of The Erode College of Pharmacy and Research Institute, Erode, Tamil Nadu, INDIA for providing necessary facilities to carry out the research work.

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Authors and Affiliations

  1. Department of Pharmacology, The Erode College of Pharmacy, Veppampalayam, Vallipurathampalayam (Po), Erode, Tamil Nadu, 638112, India

    Venugopalan Rajesh

  2. Department of Pharmacology, Devaki Amma Memorial College of Pharmacy, Malappuram District, Chelembra, Kerala, 673634, India

    Mohanan Mridhulmohan

  3. Department of Pharmaceutical Analysis, The Erode College of Pharmacy, Veppampalayam, Vallipurathampalayam (Po), Erode, Tamil Nadu, 638112, India

    Subramanian Jayaseelan

  4. Department of Pharmaceutical chemistry, The Erode College of Pharmacy, Veppampalayam, Vallipurathampalayam (Po), Erode, Tamil Nadu, 638112, India

    Palanivel Sivakumar

  5. Department of Pharmaceutics, The Erode College of Pharmacy, Veppampalayam, Vallipurathampalayam (Po), Erode, Tamil Nadu, 638112, India

    Vellaiyachamy Ganesan

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  1. Venugopalan Rajesh
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Correspondence to Venugopalan Rajesh.

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This study did not involve endangered or protected species. No specific permissions were required for the activities involved in this study. All experimental manipulations (behavioral analysis, fear conditioning, cognitive evaluation) were conducted according to the principles of the Institutional Ethical Committee, The Erode College of Pharmacy, Erode, Tamilnadu, India.

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Rajesh, V., Mridhulmohan, M., Jayaseelan, S. et al. Mefenamic Acid Attenuates Chronic Alcohol Induced Cognitive Impairment in Zebrafish: Possible Role of Cholinergic Pathway. Neurochem Res 43, 1392–1404 (2018). https://doi.org/10.1007/s11064-018-2554-3

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