Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice

Nora E. Gray, Jonathan A. Zweig, Maya Caruso, Jennifer Y. Zhu, Kirsten M. Wright, Joseph Quinn, Amala Soumyanath

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Centella asiatica is a medicinal plant used to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates β-amyloid (Aβ)-induced spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its in vivo mechanism of improving Aβ-related cognitive impairment. This study investigates the effects of CAW on learning, memory and executive function as well as mitochondrial function and antioxidant response in the 5xFAD model of Aβ accumulation. Seven month old 5xFAD female mice were treated with CAW (2 mg/mL) in their drinking water for two weeks prior to behavioral testing. Learning, memory and executive function were assessed using the object location memory task (OLM), conditioned fear response (CFR) and odor discrimination reversal learning (ODRL) test. Mitochondrial function was profiled using the Seahorse XF platform in hippocampal mitochondria isolated from these animals and tissue was harvested for assessment of mitochondrial, antioxidant and synaptic proteins. CAW improved performance in all behavioral tests in the 5xFAD but had no effect on WT animals. Hippocampal mitochondrial function was improved and hippocampal and cortical expression of mitochondrial genes was increased in CAW-treated 5xFAD mice. Gene expression of the transcription factor NRF2, as well as its antioxidant target enzymes, was also increased with CAW treatment in both WT and 5xFAD mice. CAW treatment also decreased Aβ-plaque burden in the hippocampus of treated 5xFAD mice but had no effect on plaques in the cortex. These data show that CAW can improve many facets of Aβ-related cognitive impairment in 5xFAD mice. Oral treatment with CAW also attenuates hippocampal mitochondrial dysfunction in these animals. Because mitochondrial dysfunction and oxidative stress accompany cognitive impairment in many pathological conditions beyond Alzheimer's disease, this suggests potentially broad therapeutic utility of CAW.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume93
DOIs
StatePublished - Dec 1 2018

Fingerprint

Centella
Executive Function
Amyloid
Antioxidants
Learning
Reversal Learning
Smegmamorpha
Discrimination Learning
Mitochondrial Genes
Memory Disorders
Medicinal Plants
Drinking Water
Fear
Hippocampus
Alzheimer Disease
Mitochondria
Oxidative Stress
Transcription Factors
Gene Expression
Water

Keywords

  • Antioxidant
  • Beta amyloid
  • Executive function
  • Mitochondrial function

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice. / Gray, Nora E.; Zweig, Jonathan A.; Caruso, Maya; Zhu, Jennifer Y.; Wright, Kirsten M.; Quinn, Joseph; Soumyanath, Amala.

In: Molecular and Cellular Neuroscience, Vol. 93, 01.12.2018, p. 1-9.

Research output: Contribution to journalArticle

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