Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice

PLoS One. 2015 Jul 10;10(7):e0131862. doi: 10.1371/journal.pone.0131862. eCollection 2015.

Abstract

Bacopa monnieri extract has been implicated in the recovery of memory impairments due to various neurological disorders in animal models and humans. However, the precise molecular mechanism of the role of CDRI-08, a well characterized fraction of Bacopa monnieri extract, in recovery of the diabetes mellitus-induced memory impairments is not known. Here, we demonstrate that DM2 mice treated orally with lower dose of CDRI-08 (50- or 100 mg/kg BW) is able to significantly enhance spatial memory in STZ-DM2 mice and this is correlated with a significant decline in oxidative stress and up regulation of the AMPA receptor GluR2 subunit gene expression in the hippocampus. Treatment of DM2 mice with its higher dose (150 mg/kg BW or above) shows anti-diabetic effect in addition to its ability to recover the spatial memory impairment by reversing the DM2-induced elevated oxidative stress and decreased GluR2 subunit expression near to their values in normal and CDRI-08 treated control mice. Our results provide evidences towards molecular basis of the memory enhancing and anti diabetic role of the Bacopa monnieri extract in STZ-induced DM2 mice, which may have therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacopa / chemistry
  • CA3 Region, Hippocampal / drug effects
  • CA3 Region, Hippocampal / metabolism*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / psychology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / psychology
  • Drug Evaluation, Preclinical
  • Gene Expression / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism
  • Mice
  • Oxidative Stress
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Spatial Memory / drug effects
  • Streptozocin

Substances

  • BESEB CDRI-08
  • Hypoglycemic Agents
  • Plant Extracts
  • Receptors, AMPA
  • Malondialdehyde
  • Streptozocin
  • glutamate receptor ionotropic, AMPA 2

Grants and funding

The authors acknowledge CSIR (37/1389/09/EMR-II), BRNS (2009/37/55/3298) Projects, Govt. of India, UGC-UPE, Faculty of Science, Banaras Hindu University and Lumen Research Foundation, Chennai, India for partial financial support.