Butea superba-induced amelioration of cognitive and emotional deficits in olfactory bulbectomized mice and putative mechanisms underlying its actions

J Pharmacol Sci. 2014;124(4):457-67. doi: 10.1254/jphs.13252fp. Epub 2014 Mar 19.

Abstract

This study investigated the effects of alcoholic extract of Butea superba (BS) on cognitive deficits and depression-related behavior using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its actions. OBX mice were treated daily with BS (100 and 300 mg/kg, p.o.) or reference drugs, tacrine (2.5 mg/kg, i.p.) and imipramine (10 mg/kg, i.p.) from day 3 after OBX. OBX impaired non-spatial and spatial cognitive performances, which were elucidated by the novel object recognition test and modified Y maze test, respectively. These deficits were attenuated by tacrine and BS but not imipramine. OBX animals exhibited depression-like behavior in the tail suspension test in a manner reversible by imipramine and BS but not tacrine. OBX down-regulated phosphorylation of synaptic plasticity-related signaling proteins: NMDA receptor, AMPA receptor, calmodulin-dependent kinase II, and cyclic AMP-responsive element-binding protein. OBX also reduced choline acetyltransferase in the hippocampus. BS and tacrine reversed these neurochemical alterations. Moreover, BS inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BS ameliorates not only cognition dysfunction via normalizing synaptic plasticity-related signaling and facilitating central cholinergic systems but also depression-like behavior via a mechanism differing from that implicated in BS amelioration of cognitive function in OBX animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butea*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Choline O-Acetyltransferase / metabolism
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Depression / drug therapy*
  • Depression / genetics
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Hippocampus / enzymology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / genetics
  • Olfactory Bulb / surgery*
  • Phosphorylation / drug effects
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Synapses / physiology

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Plant Extracts
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Choline O-Acetyltransferase
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2