ABSTRACT
Objective Parkinson's disease( PD) is a common chronic neurodegenerative disease,with four major symptoms of resting tremor, muscle rigidity, slow motion and postural balance disorder?The pathogenesis of Parkinson's disease is still unknown?A large number of studies suggested that may be the result of the interaction of genetic factors,environmental factors,aging,immune factors,specifically involved in oxidative stress,mitochondrial damage,and other mechanisms?There were 50% patients characterized by tremors,tremor is the most difficult symptoms to treat of PD, but the mechanism is still under controversial, so it ’ s of great significance to understand the generation of PD tremor, which helps to promote the clinical treatment and diagnosis.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of P38 mitogen-activated protein kinase (P38 MAPK) signaling pathway in regulating the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) in the substantia nigra (SN) of a mouse model of Parkinson's disease (PD).</p><p><b>METHODS</b>C57BL/6N mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish an subacute PD model, and the behavioral changes of the mice were observed. Immunohistochemistry and Western blotting were employed to detect the expressions of tyrosine hydroxylase (TH), NF-κB, iNOS and phosphorylated P38 (p-P38) in the midbrain before and after treatment with SB203580.</p><p><b>RESULTS</b>Compared with the control mice, the PD mouse models presented with typical symptoms of PD and showed significantly increased number of p-P38-, NF-κB-, and iNOS-positive cells in the SN area (P<0.01) with significantly reduced number of TH-positive neurons (P<0.01). After SB203580 treatment, the number of p-P38-, NF-κB-, and iNOS-positive cells was reduced obviously (P<0.01) and the number of TH-positive neurons in the SN increased significantly in the PD model mice (P<0.01).</p><p><b>CONCLUSION</b>P38 MAPK signaling pathway may play an important role in modulating NF-κB and iNOS expression in the SN in the early stage of MPTP-induced subacute PD, and SB203580 can inhibit P38 signaling pathway to protect the DA neurons in PD model mice.</p>
Subject(s)
Animals , Mice , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Disease Models, Animal , Imidazoles , MAP Kinase Signaling System , Mice, Inbred C57BL , Metabolism , NF-kappa B , Metabolism , Neurons , Nitric Oxide Synthase Type II , Metabolism , Parkinson Disease , Metabolism , Phosphorylation , Pyridines , Substantia Nigra , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
Objective To evaluate expression and significance of TLR4 and NF-κB on inflammatory injure after intracerebral hemorrhage in rats .Methods 60 Sprague Dawley maleness rats were randomly divided into Sham group ,12 h ,24 h ,72 h and 7 d af-ter ICH group(12 s) .The ICH was induced by injection of autologous blood in rats .The behavioral changes were detected by neu-rologic deficit score .The water content of the brain was used to evaluate brain edema changes .Number of TLR4 and NF-κB positive cells by Nissl staining and the expression of protein determined by immunohistochemistry and Western blot .Results After ICH 12 h ,expression of TLR4 and NF-κB positive cells around the hematoma were expressed ,with the extension of the time ,expression was gradually increasing ,and after ICH 72 h the expression of protein were the highest .Cerebral edema and severe neurological damage occurred .Western blot shows the amount of TLR4 expression and NF-κB were in line with the result .Conclusion After in-tracerebral hemorrhage in rat causing inflammatory injure of brain tissue around the hematoma .TLR4 may activate the expression of NF-κB involved in the secondary inflammatory injure after intracerebral hemorrhage in rats .
ABSTRACT
Objective To investegate the effect of phosphorylated-P38 MAPK(mitogen-activated protein kinase) on the expression of caspase-3 in the substania nigra (SN) of MPTP-induced mouse model of(PD). Methods Mice were randomly divided into MPTP model group, which were treated with MPTP and inhibitor group. Once a day for 5 days; control group was treated with saline and DMSO as much as the model group received per day for 5 days. The behavioral were observed, immunohistochemistry and Western blot for TH, caspase-3 and phosphorylation of P38 MAPK were used to observe the change of positive cell number and the expression level in the SN of midbrain. Results Compared with the mice in control group, the model group showed typical symtoms of PD with decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respec-tively(P<0.01) , the numbers of caspase-3 and phosphorylation of P38 MAPK immunoreactive cells and their protein level in the SN of the midbrain increased markedly (P<0.01). After giving SB203580, the above changes were reduced obviously (P <0. 01). Conclusion In the mouse model of subacute Parkinson's disease induced by MPTP, phosphorylated-P38 MAPK regulated caspase-3 in the SN of midbrain, the specific P38 MAPK inhibitor SB203580 is neurologically oprotective to the mouse model.