Centella asiatica enhances hippocampal mitochondrial function and improves learning, memory and executive function in a mouse model of Alzheimer's Disease
Nora E Gray1, Jon A Zweig1, Maya Caruso1, Marjoen D. Martin1, Jennifer Y. Zhu1, Joseph F Quinn1,2, Amala Soumyanath1 1Department of Neurology, Oregon Health and Science University, Portland, OR, USA 97239 2Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), VA Portland Healthcare System, Portland, OR, USA 97239
Centella asiatica is a memory-enhancing medicinal plant the water extract of which (CAW) has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Our lab has found that CAW also increases the expression of mitochondrial and antioxidant genes in the brains of healthy aged mice and can improve mitochondrial function in hippocampal neurons isolated from both healthy and -amyloid (A)-overexpressing mice. Here we explore the effects of CAW on mitochondrial function and cognitive performance in an in vivo model of A accumulation. Seven month old 5xFAD mice and wild-type littermates were treated with CAW (2mg/mL) in their drinking water for two weeks prior to behavioral testing. Learning, memory and executive function were assessed using the conditioned fear response test (CFR), object location memory task (OLM) and odor discrimination reversal learning (ODRL) test. Brain expression of mitochondrial, antioxidant and synaptic genes was evaluated and hippocampal mitochondrial were isolated and profiled used the Seahorse XF analyzer. CAW improved the performance of 5xFAD mice in all behavioral tests suggesting effects on multiple brain regions. The A-induced impairments in basal and maximal respiration in hippocampal mitochondria was also mitigated in CAW-treated animals. CAW also increased expression of synaptic, mitochondrial and antioxidant genes in the brains of 5xFAD mice. These data show that CAW attenuates multiple facets of A-related cognitive impairment and can improve mitochondrial bioenergetics in the brains of treated animals and activate the endogenous antioxidant response pathway. While it remains to be seen whether these mitochondrial, antioxidant and cognitive effects are directly related, the fact that mitochondrial dysfunction and oxidative stress also accompany cognitive impairment in many pathological conditions beyond Alzheimer's disease could suggests a broad therapeutic utility of CAW.
Credits: None available.
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