| Summary: | 博士 === 大葉大學 === 生物產業科技學系 === 103 === Parkinson's disease (PD) is a highly prevalent neurodegenerative disorder. In addition to motor dysfunctions, cognitive impairment and dementia are seen in a high percentage of PD patients.
The proportion of PD patients with dementia is 25 ~ 30%, up to six times higher than in healthy people. Emotional changes, for example, increased anxiety levels, visuospatial dysfunctions, and impairment of facial recognition and object discrimination. Our study show that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, microglial activation in the SNc and hippocampus, and cell loss in the hippocampal CA1 area. With regard to behavior, an increase in anxiety-like behavior and impairment of object recognition were observed during the fourth week after MPTP lesioning. MPTP-lesioned rats are therefore proposed as a useful tool for assessing the ability of pharmacological agents to prevent recognition deficits in PDD.
Hyperactivation of N-methyl-D-aspartate receptors (NMDARs) leads to neuronal excitotoxicity and is suggested to play a role in many brain disorders, Lowdose of D-cycloserine (DCS), a partial agonist of glycine binding site on N-methyl-D-aspartate (NMDA) receptors, can facilitate extracellular-signal-regulated kinase 1/2 (ERK1/2) activity in the amygdala and modulate emotional behavior. Our data has been found indicating different sensitivities of p-ERK1/2 and behavioral responses to the treatment of DCS between high open arm (HOA) and low open arm (LOA) rats. The results suggest that the activity of NMDA receptor-mediated ERK1/2 signaling is mediated by individual behavioral differences which are related to the antidepressant-like activity of DCS. This study provides first insight into the pathophysiological role of ERK signaling with regard to individual differences in emotional behavior.
The Genet that code for NMDAR subunits N-methyl-d-aspartate 1 and 2B (GRIN1 and GRIN2B) and Parkinson’s disease (PD) remains unclear. We also study this gene from Parkinson patients. In conjunction with putative low-risk genotypes for the GRIN1 gene, the GRIN2B C366G variant was significantly associated with reduced PD risk compared with the homozygous genotype 366CC (OR = 0.38, 95% CI = 0.17 ~ 0.93, p = 0.033). A synergistic effect on risk reduction was observed in subjects who carried multiple polymorphisms of GRIN1 and the GRIN2B C366G polymorphism (OR = 0.78, 95% CI = 0.59 ~ 1.02, p trend = 0.073). Our results suggest that polymorphisms in the GRIN1 and GRIN2B genes may serve as potential biomarkers for a reduced risk of PD among the Chinese population in Taiwan.
We also study the association risk of stroke in Parkinson disease patient, all data were obtained from the National Health Insurance (NHI) claim database, we collect the age and sex match control group and follow up the stroke event in the two groups. We also analysis the other risk factors: hypertension, diabetes, cardiovascular disease, hyperlipidemia. The result revealed the Parkinson disease group concomitant higher rate of Diabetes, Hypertension, Cardiovascular disease and Hyperlipidemia. The lower income level also higher risk of stroke. The accumulation incidence rate of stroke was 26.61% in Parkinson Disease group compare to 13.55% in control group. The Kaplan-Meire survival analysis for free of stroke rate, the control group had higher free stroke rate compare to Parkinson Disease group. This result suggest Parkinson disease patient had higher risk of stroke.
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