P38 MAPK signaling pathway regulates nuclear factor-κB and inducible nitric oxide synthase expressions in the substantia nigra in a mouse model of Parkinson's disease / 南方医科大学学报

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>