Investigation Into the Effects of Tenilsetam on Markers of Neuroinflammation in GFAP-IL6 Mice

Pharm Res. 2018 Jan 5;35(1):22. doi: 10.1007/s11095-017-2326-9.

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.

Keywords: alzheimer’s disease; anti-inflammatory drug; glycation; methylglyoxal; microglia; tumour necrosis factor-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Biomarkers / metabolism
  • Cerebellum / drug effects
  • Cerebellum / pathology
  • Chronic Disease
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / pathology
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Pyruvaldehyde / metabolism
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Interleukin-6
  • Piperazines
  • Thiophenes
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Pyruvaldehyde
  • tenilsetam