P38MAPK pathway regulates COX-2 and caspase-3 expression in a mouse model of Parkinson disease / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of p38 mitogen-activated protein kinase (p38MAPK) on the expression of COX-2 and caspase-3 in the substania nigra (SN) of mice with MPTP-induced Parkinson disease (PD).</p><p><b>METHODS</b>C57BL/CN mice were treated with MPTP to prepare a subacute PD model, and their behavioral changes following the treatment were observed. Immunohistochemistry and Western blotting were performed to detect the expression of tyrosine hydroxylase (TH), COX-2 and phosphorylation of P38MAPK in the SN and their changes following treatment with SB203580, a specific inhibitor of P38MAPK.</p><p><b>RESULTS</b>The 7-day model group showed typical symptoms of PD with decrements of TH-positive neurons and TH protein level in the SN of the midbrain by about 65% and 75%, respectively (P<0.01). In the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK-immunoreactive cells and their protein levels in the SN increased markedly with obvious loss of TH-positive neurons. Administration of SB203580 obviously lessened the above changes (P<0.01).</p><p><b>CONCLUSION</b>P38MAPK regulates the inflammation and apoptosis in the SN of the mouse model of subacute PD, and SB203580 may provide some neuroprotective effect.</p>