scholarly journals Zonisamide Enhances Motor Effects of Levodopa, Not of Apomorphine, in a Rat Model of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Haruo Nishijima ◽  
Yasuo Miki ◽  
Shinya Ueno ◽  
Masahiko Tomiyama

Zonisamide is a relatively recent drug for Parkinson’s disease. Multiple hypotheses have been proposed to explain the antiparkinsonian effects of zonisamide. However, it is still unclear whether the effect of zonisamide is mainly due to dopaminergic modification in the striatum, or if zonisamide works through nondopaminergic pathways. We conducted the present study to determine the mechanism that is mainly responsible for zonisamide’s effects in Parkinson’s disease. We examined the effects of zonisamide on motor symptoms in a hemiparkinsonian rat model when administered singly, coadministered with levodopa, a dopamine precursor, or apomorphine, a D1 and D2 dopamine receptor agonist. We used 6-hydroxydopamine-lesioned hemiparkinsonian rats, which were allocated to one of five groups: 14 rats received levodopa only (6 mg/kg), 12 rats received levodopa (6 mg/kg) plus zonisamide (50 mg/kg), six rats received apomorphine only (0.05 mg/kg), six rats received apomorphine (0.05 mg/kg) plus zonisamide (50 mg/kg), and six rats received zonisamide only (50 mg/kg). The drugs were administered once daily for 15 days. We evaluated abnormal involuntary movement every 20 min during a 3 h period following the injection of drugs on treatment Days 1, 8, and 15. Western blot analyses for dopamine decarboxylase and vesicular monoamine transferase-2 were performed using striatal tissues in the lesioned side of rats in the levodopa only group (n = 6) and levodopa plus zonisamide group (n = 4). Levodopa-induced abnormal involuntary movement was significantly enhanced by coadministration of zonisamide. In contrast, zonisamide had no effect on apomorphine-induced abnormal involuntary movement. Zonisamide monotherapy did not induce abnormal involuntary movement. Zonisamide did not affect striatal expression of dopamine decarboxylase or vesicular monoamine transferase-2. In conclusion, zonisamide appears to generate its antiparkinsonian effects by modulating levodopa-dopamine metabolism in the parkinsonian striatum.

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Napatr Sriraksa ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura ◽  
Somsak Tiamkao ◽  
Kamoltip Brown ◽  
...  

Oxidative stress has been reported to induce cognitive impairment in Parkinson's disease. This paper aimed to determine the effect of quercetin, a substance possessing antioxidant activity, on the cognitive function in a rat model of Parkinson's disease. Male Wistar rats, weighing 200–250 g, were orally given quercetin at doses of 100, 200, 300 mg/kg BW once daily for a period of 14 days before and 14 days after the unilateral lesion of right substantia nigra induced by 6-hydroxydopamine (6-OHDA). Their spatial memory was assessed at 7 and 14 days of treatment and neuron density was determined, malondialdehyde (MDA) level, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated at the end of the experiment. In addition, the activity of acetylcholinesterase (AChE) was also measured. It was found that all doses of quercetin enhanced spatial memory. Therefore, it is suggested that the cognitive-enhancing effect of quercetin occurs partly because of decreased oxidative damage resulting in increased neuron density.


PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172394 ◽  
Author(s):  
Robert Westphal ◽  
Camilla Simmons ◽  
Michel B. Mesquita ◽  
Tobias C. Wood ◽  
Steve C. R. Williams ◽  
...  

2010 ◽  
Vol 1328 ◽  
pp. 139-151 ◽  
Author(s):  
Mohd.Moshahid Khan ◽  
Ajmal Ahmad ◽  
Tauheed Ishrat ◽  
M. Badruzzaman Khan ◽  
Md. Nasrul Hoda ◽  
...  

Author(s):  
Rayanne Poletti Guimarães ◽  
Danilo Leandro Ribeiro ◽  
Keila Bariotto dos Santos ◽  
Lívea Dornela Godoy ◽  
Mirella Rosine Corrêa ◽  
...  

Synapse ◽  
2018 ◽  
Vol 73 (3) ◽  
pp. e22077 ◽  
Author(s):  
Steven Vetel ◽  
Sophie Sérrière ◽  
Johnny Vercouillie ◽  
Jackie Vergote ◽  
Gabrielle Chicheri ◽  
...  

Medicina ◽  
2011 ◽  
Vol 47 (10) ◽  
pp. 79 ◽  
Author(s):  
Sergejs Isajevs ◽  
Darja Isajeva ◽  
Ulrika Beitnere ◽  
Baiba Jansone ◽  
Ivars Kalvinsh ◽  
...  

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM). Material and Methods. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay. Results. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values. Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.


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