This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate-limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have very l...

Cerebellar granule neurons (CGNs) extrasynaptically express GABA(A) receptors containing alpha(6)beta(x)delta subunits, which mediate tonic inhibitory currents. Although it has been shown that the function of these receptors is potently and directly enhanced by ethanol, this finding has not been reproducible across different laboratories. In outbred Sprague-Dawley rats, a naturally occurring ar...

G-protein-coupled receptor (GPR) 3 is a member of the GPR family that constitutively activates adenylate cyclase. We have reported that the expression of GPR3 in cerebellar granular neurons (CGNs) contributes to neurite outgrowth and modulates neuronal proliferation and survival. To further identify its role, we have analyzed the precise distribution and local functions of GPR3 in neurons. The ...

In this study, the effects of melatonin on MPP+ -treated cerebellar granule neurons (CGNs) in culture were investigated. Results showed that MPP+ treatment significantly decreased cell viability and increased the apoptotic cell population at 24 and 48 hr. Calpain and caspase-3 activation was also determined, with results showing a strong increase in calpain (74%) and caspase 3 activity (70%), a...

Wnt signaling regulates self-renewal and fate commitment of stem and progenitor cells in development and homeostasis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a co-receptor for Wnt signaling that marks highly proliferative stem and progenitor cells in many epithelial tissue types. Wnt signaling instructs neural developmental and homeostatic processes; however, Lgr5 ...

Recent studies demonstrate that lithium and valproic acid (VPA), two commonly used mood-stabilizing drugs, have neuroprotective effects against a variety of insults. Inhibition of the pro-apoptotic enzyme, glycogen synthase kinase-3P (GSK-3P), was suggested to be the mechanism of action of neuroprotection for both drugs. In this study, we tested if lithium and VPA could protect cultured cerebel...

Lithium (Li), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has used to attenuate thecannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this areunclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2)and downstream GSK-3β pathways in the development of cannabinoid-induced dependence. Thisis mediated through cannab...

Lithium (Li), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has used to attenuate thecannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this areunclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2)and downstream GSK-3β pathways in the development of cannabinoid-induced dependence. Thisis mediated through cannab...

Exposure of mouse cerebellar granule neurons (CGNs) to domoic acid induced cell death, either by apoptosis or by necrosis, depending on its concentration. Necrotic damage predominated in response to domoic acid above 0.1 microM. In contrast, cell injury with apoptotic features (assessed by Hoechst staining and DNA laddering assay) was evident after exposure to lower concentrations of domoic aci...

Phosphorylation is considered a main mechanism modulating nNOS (neuronal nitric oxide synthase) function to reduce NO production. In the present study, the effects of nNOS phosphorylation on redox signalling, including that of NO, ROS (reactive oxygen species), and 8-nitro-cGMP (8-nitroguanosine 3',5'-cyclic monophosphate), a downstream messenger of redox signalling, were investigated. In vitro...