Font Size: a A A

The Experimental Investigation Of The Effect Of PDTC On The Expression Of NF-κB In Substantia Nigra Of Parkinson's Disease Mouse Model By MPTP

Posted on:2006-10-10Degree:MasterType:Thesis
Country:ChinaCandidate:Z B PeiFull Text:PDF
GTID:2144360155951229Subject:Neurology
Abstract/Summary:PDF Full Text Request
Objective (1)To observe whether or not there are the expression and activation of nuclear factor-κappaB(NF-κB) in substantia nigra of Parkinson's disease mouse model by the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP). (2)To observe the effect of NF-κB on the happening and development of Parkinson's disease(PD) mouse model by MPTP. (3)To obseve the effect of nuclear factor-κappaB antagonist pyrrolidine dithiocarbamate (PDTC) on dopaminergic neurons in substantia nigra pars compacta(SNpc) when PDTC was pre-injected into mouse every time before the neurotoxin MPTP was injected to make Parkinson's disease mouse model. Methods The sixty normal, healthy, eight- to twelve-week-old male C57/BL mice were divided into four test groups(TG), four prevention groups(PG) and four normal groups(NG)( 5 per set). All mice were fed with same things at same time. Test group mice were treated with MPTP, Prevention group mice were treated with MPTP and PDTC, Normal group mice were treated with 0.9% physiology saline. MPTP was administered in 0.9% physiology saline at a dose of 30 mg·kg-1 i.p. at 24-hour intervals for one, three, seven and fourteen doses separately in TG mice in order to make PD mice models.PG mice were treated with MPTP administered in 0.9% physiology saline at a dose of 30 mg·kg-1 after half an hour treated with PDTC administered in 0.9% physiology saline at a dose of 40 mg·kg-1 i.p. at 24-hour intervals for one, three, seven, fourteen doses separately.NG mice were treated with 0.9% physiology saline i.p. at 24-hour intervals for one, three, seven, fourteen doses in same quantity separately,too. Before administered from means of action, every C57/BL mouse was measured their time of pole test and watched whether or not there are behaviors of Parkinson's disease, and after administered for one, three, seven, fourteen doses, every C57/BL mouse was measured their time of pole test and watched whether or not there are behaviors of PD from means of action, too. Then immunohistochemistry adopting streptavidin-biotin-peroxidase complex ,namely SABC was performed on serial sections of the midbrains for nuclear factor-κappaB p65and tyrosine hydroxylase(TH) in order to measure and know expression of NF-κappaB p65 protein,the count of NF-κappaB p65 positive cell , phenomenon of dislocation into nucleus of NF-κappaB ,the count of TH positive neurons and fibers at original locationin substantia nigra of every mouse after administered for one, three, seven, fourteen doses separately. Phenomenon of lost cells in SN were observed on morphology by Pischingert's methyleneblue staining (Nissl staining) and HE staining (nervous pathology) in SN of every mouse after administered for one, three, seven, fourteen doses separately. The possible relations between NF-κappaB and PD were able to be knowed from many levels and many angles like expression of NF-κappaB p65 protein, the count of NF-κappaB p65 positive cell, dislocation into nucleus of NF-κappaB, the count of TH positive neurons and fibers in SN, means of action and morphology and so on. Results (1)results of means of action: No significant differences (p>0.05) were found in time difference of pole test among TG,PG and NG mice after administered for one dose, no every group mice did manifest abnormal behaviors of Parkinson's disease such as mouse's forelimbs raised and tremored and mouse move slowly. After administered for three, seven, fourteen doses separately, time difference of pole test of TG mice increased more than of correspondence PG and NG mice, Significant differences(p<0.05) were found in time difference of pole test between TG and correspondence NG mice, so did TG and correspondence PG group mice. Some TG mice began to manifest impermanent abnormal behaviors of PD since mice were on the third injected the neurotoxin MPTP. Abnormalbehaviors of PD were strong more and more and lasted longer and longer after TG mice were injected every time since the third. No significant differences (p>0.05) were found in time differe...
Keywords/Search Tags:1-methyl-4-phenyl-1,2,3,6tetrahydropyridine(MPTP), Parkinson's disease, nuclear factor-κappaB(NF-κB)
PDF Full Text Request
Related items