Neuronal Nitric Oxide synthase regulates the expression of EAAT4 and GAD65/67 in the murine cerebellum
type: CreativeWork
description: The cerebellum is a brain structure that is responsible for coordinating voluntary movement such as balance, coordination, and posture. Purkinje neurons (PNs) are the sole GABAergic output from the cerebellar cortex and receive major excitatory inputs via parallel fibers (PFs) that produce high levels of nitric oxide (NO) via neuronal nitric oxide synthase (nNOS). Previous studies demonstrate that nNOS/NO signaling is crucial for PF-PN synaptic transmission. This study sought to examine nNOS/NO signaling regulation of excitatory amino acid transporter 4 (EAAT4) on PN dendrites and glutamic acid decarboxylase (GAD) expression/function between sexes by using wildtype (WT) and nNOS-/- mice at different postnatal developmental time points. This study revealed that there are gene- and sex-dependent differences in GABA concentration in the cerebellum during early postnatal development. Additionally, there is decreased EAAT4 expression in male nNOS-/- mice. Lastly, there is decreased GAD65/67 expression in both male and female nNOS-/- nice compared to age-matched WT mice. Our results provide new knowledge of NO regulation of cerebellar synaptic transmission, which may advance the development of cerebellar ataxia therapeutics.
abstract: The cerebellum is a brain structure that is responsible for coordinating voluntary movement such as balance, coordination, and posture. Purkinje neurons (PNs) are the sole GABAergic output from the cerebellar cortex and receive major excitatory inputs via parallel fibers (PFs) that produce high levels of nitric oxide (NO) via neuronal nitric oxide synthase (nNOS). Previous studies demonstrate that nNOS/NO signaling is crucial for PF-PN synaptic transmission. This study sought to examine nNOS/NO signaling regulation of excitatory amino acid transporter 4 (EAAT4) on PN dendrites and glutamic acid decarboxylase (GAD) expression/function between sexes by using wildtype (WT) and nNOS-/- mice at different postnatal developmental time points. This study revealed that there are gene- and sex-dependent differences in GABA concentration in the cerebellum during early postnatal development. Additionally, there is decreased EAAT4 expression in male nNOS-/- mice. Lastly, there is decreased GAD65/67 expression in both male and female nNOS-/- nice compared to age-matched WT mice. Our results provide new knowledge of NO regulation of cerebellar synaptic transmission, which may advance the development of cerebellar ataxia therapeutics.
author: Jassal, Gurneet
language: en_ca
keywords: Cerebellum, Neuronal Nitric Oxide Synthase, Nitric Oxide, Purkinje Neuron, Excitotoxicity
date published: 2022-12-16
date modified: 2026-07-27T21:56:14Z
provider: Western University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: The University of Western Ontario

PropertyValue
property ID: Handle
value: https://hdl.handle.net/20.500.14721/32725