Publication Date

2016-4

Document Type

Honors Thesis

Department

Neuroscience

Keywords

Withania somnifera, Electrophysiology, Glycine-Receptors, Traditional medicine, Neurotransmitter uptake inhibitors, Neural transmission, Xenopus laevis, Glycine receptor, Indigenous medicine, Inhibitory neurotransmission

Abstract

The human glycine receptor, a ligand-gated ion channel permeable to chloride, is a major player in inhibitory neurotransmission within the spinal cord and brainstem. Inhibitory neurotransmission is crucial in regulating circuits within the nervous system. The oocytes of Xenopus laevis, the African clawed frog, provide an isolated environment for modeling the chemical modulation of specific neurotransmitter receptors. Oocytes in this experiment were injected with plasmid DNA enabling them to express the homopentameric alpha-1 human glycine receptor (hGlyR). Oocytes expressing this receptor were voltage-clamped and exposed via superfusion to an extract derived from the root powder of Withania somnifera (WS). WS is an herb used in traditional Indian medicine to treat anxiety, insomnia, neurodegenerative disorders, and digestive conditions, as well as to enhance immune function. Although many of the chemical components of WS are known, the active chemical responsible for these medicinal effects has not been identified. Recent evidence shows that both the GABAA and GABAA-ρ receptors are directly activated by preparations of WS root powder. Like the human glycine receptor, these receptors are mediators of fast inhibitory neurotransmission and members of the "Cys-loop family" of receptors, in addition to being structurally homologous to the glycine receptor. These similarities and the agonist effect of WS on GABA receptors make the glycine receptor another likely site of modulation. Electrophysiological data suggest that WS functions as a partial agonist and competitive antagonist of the hGlyR, which may support its use as an anxiolytic.

Language

English

Comments

43 pages : color illustrations. Honors project, Smith College, 2016. Includes bibliographical references (pages 41-43)

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