title: Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.
abstract: The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer's disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer's disease.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: grayn@ohsu.edu.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Gray
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Zweig
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Murchison
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Caruso
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Matthews
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Kawamoto
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Harris
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA; Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Amala
authors.initials: A
authors.lastname: Soumyanath
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D028041:Centella / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides
keywords: Amyloid-β; Centella asiatica; Neuroprotection; Synaptic health