The anti-inflammatory effects of cytokine suppressive anti-inflammatory drugs Tenilsetam and Longvida curcumin on microglia numbers in the GFAP-IL6 mouse model

Abstract

Chronic neuroinflammation has been observed to be a key factor in the progress of neurodegenerative diseases including Alzheimer's disease (AD). Microglia serve as resident macrophages within the central nervous system (CNS) and become activated upon contact with entities that are released from dying neurons during neurodegenerative processes, these include neuro-filaments, AI² aggregates and tau containing neurofibrillary tangles, exposed naked DNA and oligodendrocytic myelin fragments. This prompts microglial and astrocyte activation which ultimately causes further neuronal damage including synaptic depredation. Neuronal tissue within the central nervous system can become particularly vulnerable to chronic neuroinflammation as a vicious self-perpetuating cycle of inflammation causes chronic neuronal decay. It is thought that preventing and or reducing chronic neuroinflammation by anti-inflammatory drugs will reduce chronic neuroinflammation, thus disrupting the cycle of microglial and astrocyte activation and resulting neurodegeneration. This thesis compares the short and long-term anti-inflammatory properties of two drugs: The nootropic drug Tenilsetam (±)-3-(2-thienyl)-2-piperazinone (CAS 997, Tenilsetam) and the herbal spice curcumin (1E,6E)-1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) (by Verdure Sciences) in the GFAP-IL6 mouse model. This research project found that Tenilsetam decreased the total number of TSPO+ microglia in the hippocampus of 8-month-old GFAP-IL6 mice along with Iba1+ microglia in the cerebellum and hippocampus of GFAP-IL6 mice at 8 months of age and in the cerebellum at 18 months of age. Microglial density in the cerebellum of GFAP-IL6 mice decreased to a similar level after both 5 and 15 months of feeding, with volume loss prevented in by Tenilsetam at 8 months. Longvida curcumin was found to decrease the total number of Iba-l+ microglia in the cerebellum of GFAP-IL6 mice at 8 months of age. When compared to Tenilsetam, Longvida curcumin had statistically similar Iba-1+ microglial numbers in the cerebellum of GFAP-IL6 mice at 8 months of age. Comparing these results and considering the efficacy of Tenilsetam, it can be inferred that due to the similarity in microglial population within the same genotype, Longvida curcumin is as effective as Tenilsetam at preventing neuroinflammation in the cerebellum of GFAP-IL6 mice at 8 months of age.

Date of Award	2019
Original language	English