Erika Gyengesi1,2, Huazheng Liang3,4, Christopher Millington1, Sandra Sonego1, Daniel Sirijovski5, Dhanushka Gunawardena1, Karthik Dhananjayan1, Madhuri Venigalla1, Garry Niedermayer5, Gerald Münch1,2,6. 1. Department of Pharmacology, School of Medicine, Western Sydney University, Building 30, Goldsmith Ave, Campbelltown, NSW, 2560, Australia. 2. Molecular Sciences Research Group, School of Medicine, Western Sydney University, Campbelltown, Australia. 3. Department of Pharmacology, School of Medicine, Western Sydney University, Building 30, Goldsmith Ave, Campbelltown, NSW, 2560, Australia. a.liang@westernsydney.edu.au. 4. Molecular Sciences Research Group, School of Medicine, Western Sydney University, Campbelltown, Australia. a.liang@westernsydney.edu.au. 5. School of Science and Health, Western Sydney University, Campbelltown, Australia. 6. National Institute of Complementary Medicine, Western Sydney University, Campbelltown, Australia.
Abstract
PURPOSE: To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6 mouse. METHODS: From 3 months of age, GFAP-IL6 mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1+ microglia, TSPO+ cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively. RESULTS: Tenilsetam decreased the total number of Iba-1+ microglia in both the cerebellum and the hippocampus of GFAP-IL6 mice at 8 months and in the cerebellum at 18 months. In the cerebellum, it decreased the density of microglia in GFAP-IL6 mice to a similar level after 5 and 15 months' feeding. Tenilsetam prevented the volume loss of the cerebellum at 8 months. It also significantly decreased TNF-α in the cerebellum of GFAP-IL6 mice to a similar level of WT mice after 15 months of feeding. CONCLUSION: Tenilsetam has anti-inflammatory effects evidenced by the decreased number of microglia in both the cerebellum and hippocampus, and decreased TNF-α levels in the GFAP-IL6 Tenilsetam fed animals.
PURPOSE: To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6mouse. METHODS: From 3 months of age, GFAP-IL6mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1+ microglia, TSPO+ cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively. RESULTS:Tenilsetam decreased the total number of Iba-1+ microglia in both the cerebellum and the hippocampus of GFAP-IL6mice at 8 months and in the cerebellum at 18 months. In the cerebellum, it decreased the density of microglia in GFAP-IL6mice to a similar level after 5 and 15 months' feeding. Tenilsetam prevented the volume loss of the cerebellum at 8 months. It also significantly decreased TNF-α in the cerebellum of GFAP-IL6mice to a similar level of WT mice after 15 months of feeding. CONCLUSION:Tenilsetam has anti-inflammatory effects evidenced by the decreased number of microglia in both the cerebellum and hippocampus, and decreased TNF-α levels in the GFAP-IL6Tenilsetam fed animals.
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