L-DOPA modulation of corpus striatal dopamine and dihydroxyphenylacetic acid output from intact and 6-OHDA lesioned rats.
*Sympathectomy; 3; 4-Dihydroxyphenylacetic Acid/*metabolism; Animals; Antiparkinson Agents/*pharmacology; Chemical; Corpus Striatum/drug effects/*metabolism; Dopamine/*metabolism; Levodopa/*pharmacology; Male; Oxidopamine; Rats; Sprague-Dawley; Substantia Nigra/drug effects/metabolism
In the present report we examined the differences in in vitro dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) efflux from the corpus striatum (CS) of intact versus 6-hydroxydopamine (6-OHDA) lesioned (in substantia nigra) male rats in response to different doses of two pulse infusions of L-dihydroxyphenylalanine (L-DOPA). In the first experiment, we tested the effects of two 20-min infusions of 5 uM L-DOPA. In the second experiment we repeated this protocol using 50 uM
Xu K; Dluzen D E
Journal of neural transmission (Vienna, Austria : 1996)
1996
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/BF01271190" target="_blank" rel="noreferrer noopener">10.1007/BF01271190</a>
The anti-parkinsonian drug zonisamide reduces neuroinflammation: Role of microglial Nav 1.6.
Female; Humans; Male; Animals; Mice; Aged; *gp91(phox); *Microglia; *MPTP; *Na(v)1.6; *Neuroinflammation; *Parkinson's disease; *TNF-alpha; *Voltage-gated sodium channels; *Zonisamide; Inflammation/metabolism; Neuroprotective Agents/pharmacology; Antiparkinson Agents/*pharmacology; Inbred C57BL; Microglia/drug effects/*metabolism; NAV1.6 Voltage-Gated Sodium Channel/*biosynthesis; Parkinsonian Disorders/*metabolism/pathology; Zonisamide/*pharmacology
Parkinson's disease (PD), the second most common age-related progressive neurodegenerative disorder, is characterized by dopamine depletion and the loss of dopaminergic (DA) neurons with accompanying neuroinflammation. Zonisamide is an-anti-convulsant drug that has recently been shown to improve clinical symptoms of PD through its inhibition of monoamine oxidase B (MAO-B). However, zonisamide has additional targets, including voltage-gated sodium channels (Nav), which may contribute to its reported neuroprotective role in preclinical models of PD. Here, we report that Nav1.6 is highly expressed in microglia of post-mortem PD brain and of mice treated with the parkinsonism-inducing neurotoxin MPTP. Administration of zonisamide (20mg/kg, i.p. every 4hx3) following a single injection of MPTP (12.5mg/kg, s.c.) reduced microglial Nav 1.6 and microglial activation in the striatum, as indicated by Iba-1 staining and mRNA expression of F4/80. MPTP increased the levels of the pro-inflammatory cytokine TNF-alpha and gp91(phox), and this was significantly reduced by zonisamide. Together, these findings suggest that zonisamide may reduce neuroinflammation through the down-regulation of microglial Nav 1.6. Thus, in addition to its effects on parkinsonian symptoms through inhibition of MAO-B, zonisamide may have disease modifying potential through the inhibition of Nav 1.6 and neuroinflammation.
Hossain Muhammad M; Weig Blair; Reuhl Kenneth; Gearing Marla; Wu Long-Jun; Richardson Jason R
Experimental neurology
2018
2018-10
<a href="http://doi.org/10.1016/j.expneurol.2018.07.005" target="_blank" rel="noreferrer noopener">10.1016/j.expneurol.2018.07.005</a>