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Protective Effects of 1-Methylnicotinamide on Aβ1–42-Induced Cognitive Deficits, Neuroinflammation and Apoptosis in Mice

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Abstract

The neurotoxicity of Aβ peptides has been well documented, but effective neuroprotective approaches against Aβ neurotoxicity are unavailable. In the present study, we investigated effects of 1-Methylnicotinamide (MNA), known as a main metabolite of nicotinamide (NA), on the impairment of learning and memory induced by Aβ and the underlying mechanisms. We found that intragastric administration of MNA at 100 or 200 mg/kg for 3 weeks significantly reversed bilateral intrahippocampal injection of Aβ1–42-induced cognitive impairments in the Morris water maze (MWM), Y-maze and Novel object recognition tests. Furthermore, MNA suppressed Aβ1–42-induced neuroinflammation, characterized by suppressed activation of microglia, decreased the expression of IL-6, TNF-α and nuclear translocation of NF-κB p65, as well as attenuated neuronal apoptosis as indicated by decreased TUNEL-positive cells and ratio of caspase-3 fragment to procaspase-3, and increased ratio of Bcl-2/Bax in the hippocampus. Our results show that MNA may ameliorate Aβ1–42-induced cognition deficits, which is involved in inhibition of neuroinflammation and apoptosis mediated by NF-κB signaling, suggesting that MNA could have potential therapeutic value for AD.

Neuroprotective affect of MNA on Aβ1–42-induced cognitive deficits.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81573413, 81773714 and 81273497 to Hao Hong, 81603113 to Su Su Tang), the Natural Science Foundation of Jiangsu Province (BK20150705 to Su Su Tang), and the Fundamental Research Funds for the Central Universities (2632017PT01).

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Authors and Affiliations

  1. Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing, 210009, China

    Lili Fu, Caihong Liu, Liang Chen, Yangge Lv, Mei Hu, Yan Long, Hao Hong & Susu Tang

  2. School of Pharmacy, Nantong University, Nantong, 226001, Jiangsu, China

    Guoliang Meng

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  1. Lili Fu
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  2. Caihong Liu
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  3. Liang Chen
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Correspondence to Hao Hong or Susu Tang.

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The National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80–23, revised, 1996) was used for the experiments and the procedures were approved by the Animal Care and Use Committee, China Pharmaceutical University.

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Fu, L., Liu, C., Chen, L. et al. Protective Effects of 1-Methylnicotinamide on Aβ1–42-Induced Cognitive Deficits, Neuroinflammation and Apoptosis in Mice. J Neuroimmune Pharmacol 14, 401–412 (2019). https://doi.org/10.1007/s11481-018-09830-1

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