Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

Life Sci. 2019 Dec 1:238:116898. doi: 10.1016/j.lfs.2019.116898. Epub 2019 Oct 11.

Abstract

Aims: Learning and memory impairment is a common symptom in the early stages of various types of dementia. It is likely to reduce the incidence of dementia with correct intervention. α-Asarone is the main bioactive substance isolated from Acorus tatarinowii Schott and has been proven to improve memory dysfunction; however, at present, the specific underlying mechanism is poorly understood. The aim of the present study was to investigate the effect of α-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice.

Main methods: A mouse model of impaired learning and memory was created by ethanol (2.0 g/kg, i.g.). α-Asarone (7.5, 15 or 30 mg/kg, i.p.) was delivered 10 min prior to ethanol administration. The behavioral effect of α-asarone was evaluated using the novel object recognition test. Glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the hippocampus were determined by ELISA, and the protein expression levels of hippocampal GluR2, NMDAR2B, SYNΙ, GLT-1 and CaMKⅡ were detected by western blotting.

Key findings: Pretreatment with α-asarone significantly improved the behavioral performance, regulated the imbalance of Glu and GABA in the hippocampus and the abnormal expression of related proteins. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu.

Significance: Our results show that the improvement in learning and memory elicited by α-asarone may providing a possible novel candidate for the prevention of learning and memory impairment in the early stages of dementia.

Keywords: Ethanol; Excitotoxicity; Glutamate; Learning and memory impairment; α-Asarone.

MeSH terms

  • Allylbenzene Derivatives
  • Animals
  • Anisoles / pharmacology*
  • Central Nervous System Depressants / toxicity*
  • Disease Models, Animal
  • Ethanol / toxicity*
  • Fibrinolytic Agents / pharmacology*
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Learning / drug effects*
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neurotransmitter Agents / metabolism

Substances

  • Allylbenzene Derivatives
  • Anisoles
  • Central Nervous System Depressants
  • Fibrinolytic Agents
  • Neurotransmitter Agents
  • asarone
  • Ethanol
  • Glutamic Acid