Plant Extracts Stimulate the Autophagy-Lysosomal Protein Clearance Pathway and Improve Brain Synapse Markers in an Explant Model of Age-Related Protein Accumulation Stress

UNCP Author/Contributor (non-UNCP co-authors, if there are any, appear on document)
Michael Fernandes de Almeida, Research Specialist (Creator)
The University of North Carolina at Pembroke (UNCP )
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Abstract: Brain aging causes gradual protein accumulation pathology as clearance systems depreciate, leading to synaptic compromise, cognitive decline, and contributing as the primary risk factor of dementia. Removal of old and damaged proteins becomes less efficient with age, Poor nutrition is thought to influence cognitive aging and a growing number of studies point to natural products and a healthy diet as avenues for promoting brain health. The aim of this study was to screen a group of plant extracts for the ability to amplify the brain’s autophagy-lysosomal protein clearance pathway and to determine if such amplification reduces synaptic decline in a brain slice model of protein accumulation stress. Using slice cultures of rat hippocampus, a brain region vulnerable to Alzheimer’s disease and aging, plant extracts (1-500 µg/ml) were applied daily for 3 days, followed by assessment for changes in synaptic markers and components of theautophagy-lysosomal pathway as compared to vehicle-treated samples. The extract-infused hippocampal slice cultures were also treated with the lysosomal inhibitor chloroquine (CQN) and tested for protection against protein accumulation stress-induced synaptic compromise. American ginseng (P. quinquefolius) and bacopa (B. monnieri) extracts markedly enhanced the lysosomal protease cathepsin B (CatB). They both produced a nearly 4-fold increase in the 30-kDa active form of CatB (CatB-30), whereas only brain tissue treated with American ginseng exhibited a correlation between CatB levels and improved measures of the synaptic protein GluR1. Small increases in CatB-30 were produced by extracts from Panax ginseng and wild blueberry (V. myrtillus). Also a primary outcome, American ginseng-treated slices were less prone to synaptic decline due to CQN-mediated protein accumulation stress. Plant extracts differentially enrich CatB in hippocampal tissue in a manner that positively influences synaptic integrity. Enhancing the autophagy-lysosomal pathway protected brain synapses in a model of age-related deficiency in protein clearance activity, suggesting a need for additional studies to test for benefits in aged animals with cognitive impairment.

Additional Information

UNCP Research and Creativity Showcase
Language: English
Date: 2019
Biology, Brain Aging, Brain Health, Protein Accumulation Pathology, Autophagy-Lysosomal Pathway, Brain Synapses, Synaptic Decline

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