EXPLORING THE EFFECT OF CENTELLA ASIATICA ON MITOCHONDRIAL BIOGENESIS IN THE MOUSE BRAIN

Abstract

Mitochondrial (MT) dysfunction correlates with amyloid beta (Aβ) accumulation and plays an integral role in neuronal death in Alzheimer's Disease (AD). Treatment with a water extract from the medicinal herb Centella asiatica(CAW) improved cognitive function of 20mo old WT and Tg2576 mice. CAW upregulated MT electron transport chain (ETC) genes in hippocampus, cortex, and cerebellum of WT animals (Tg2576 not examined). Our previous studies demonstrated an impact of CAW on MT function, and protection of SH-SY5Y and MC65 cells lines from Aβ toxicity. We hypothesize this is due to CAW's effect on mitochondrial biogenesis. Primary hippocampal neurons from WT rats were analyzed for MT gene expression via qPCR. WT C57Bl6 mice (4mo) were treated for 5wks with or without CAW in their water (approximately 200mg/kg/d) and behavioral testing performed starting at 2wks treatment. At 5 weeks, brain tissues fixed for electron microscopy (EM) were embedded in Epon/Spurrs resin. Double contrast method using uranyl acetate and lead citrate was used to stain sections and visualized by a JEOL 1400 transmission EM. MT density (number per cell section) and MT area within neural soma were analyzed using FIJI software. CAW treatment correlated with an increase in ETC genes (cytochrome B, NADH dehydrogenase 1, cytochrome C oxidase 1, ATP synthase 6) in primary rat hippocampal neurons. In CAW-treated 5mo old WT mice, behavioral testing did not show a change in cognitive function. However, analysis of EM brain sections demonstrated an increase in MT area per cell (p=0.04), proportional to an increase in neural soma cytoplasmic area (p=0.01) in CAW-treated mice. Interestingly, there was no significant change in number of MT per cell with CAW. We demonstrate an increase in MT ETC gene expression in vitro and an increase in MT and cell size of neural soma in vivo in response to CAW treatment in young WT mice. This supports our earlier work suggesting MT as a target in the cognitive effects of CAW. We propose to use EM to examine CAW's effects on MT in brains of aged WT or Tg2576 animals where greater MT dysfunction is likely.