No abstract

S100beta is a calcium-binding peptide produced by astrocytes. This protein is expressed at high levels in brain and is known as a marker of brain damage. However, little is known about the role of S100beta protein during neuronal damage caused by MPTP. To determine exactly changes of expression of S100beta protein in relation to changes of glial cells, we investigated immunohistochemically the expression of S100beta protein using MPTP-treated mice. The present study showed that tyrosine hydroxylase (TH) immunoreactivity was decreased in the striatum and substantia nigra from 5 h and 1 day after MPTP treatment, respectively. Thereafter, a severe reduction in TH immunoreactivity was observed in the striatum and substantia nigra 1, 3 and 7 days after MPTP treatment. In our double-labeled immunostaining, the number of S100-positive/GFAP-negative cells decreased from 1 day up to 7 days after MPTP treatment. In contrast, the number of double-labeled S100/GFAP-immnoreactive cells increased from 1 day up to 7 days after MPTP treatment. The number of S100beta-positive/GFAP-negative cells also decreased 3 and 7 days after MPTP treatment. In contrast, the number of double-labeled S100beta/GFAP-immunoreactive cells increased from 1 day up to 7 days after MPTP treatment. The present study demonstrates that S100beta/GFAP-positive cells may play some role in the pathogenesis of MPTP-induced dopaminergic neurodegeneration in the striatum. The present results also suggest the presence of the S100beta protein in a subpopulation of GFAP-negative astrocytes in the striatum after MPTP treatment. These results suggest that the modulation of astrocytic activation may offer a novel therapeutic strategy of Parkinson's disease.

We investigated the alteration of oligodendrocytes in comparison with that of astrocytes and microglia in the mouse striatum after MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropridine) treatment under the same conditions using Western blot analysis and Immunohistochemistry. In our Western blot analysis, four administrations of MPTP at 2-h intervals to mice produced the remarkable loss of TH (tyrosine hydroxylase) protein levels in the striatum after 3 and 7 days. In contrast, GFAP (glial fibrillary acidic protein) and Iba-1 protein in the striatum showed a significant increase of GFAP and Iba-1 protein levels 3 and 7 days after MPTP treatment. On the other hand, the levels of CNPase (2', 3'-cyclic nucleotide 3'-phosphodiesterase) protein were decreased significantly in the striatum 3 and 7 days after MPTP treatment. In our immunohistochemical study, a significant decrease in the area of expression of CNPase-positive profiles was observed in the striatum 3 and 7 days after MPTP treatment. These results demonstrate that oligodendrocytes in the striatum are damaged after MPTP treatment. Thus our present findings provide valuable information for the pathogenesis of Parkinson's disease.

We investigated the immunohistochemical alterations of the transcription nuclear factor kappa-B (NF-kappaB) and transcription factor p53 in the hippocampus after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of NF-kappaB, p53 and neuronal nuclei in the hippocampus after ischemia. Severe neuronal damage was observed in the hippocampal CA1 neurons 5 and 14 days after ischemia. In the present study, the increase of NF-kappaB immunoreactivity in glial cells and p53 immunoreactivity in neurons preceded neuronal damage in the hippocampal CA1 sector after ischemia. Thereafter, NF-kappaB immunoreactivity was induced highly in reactive astrocytes and microglia of the hippocampal CA1 sector where severe neuronal damage was observed. Our immunohistochemical study showed that pitavastatin prevented the alterations of NF-kappaB and p53 in the hippocampal CA1 sector 5 days after transient ischemia. Furthermore, our results with neuronal nuclei immunostaining indicate that pitavastatin dose-dependently prevented the neuronal cell death in the hippocampal CA1 sector 5 days after transient cerebral ischemia. These results suggest that the up-regulations of NF-kappaB in glia and p53 in neurons can cause neuronal cell death after ischemia. Our findings also support the hypothesis that NF-kappaB- and/or p53-mediated neuronal cell death is prevented through decreasing oxidative stress by pitavastatin. Thus, NF-kappaB and p53 may provide an attractive target for the development of novel therapeutic approaches for brain stroke.

We investigated the immunohistochemical alterations of parvalbumin (PV)-expressing interneurons in the hippocampus after transient cerebral ischemia in gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the damage of neurons and interneurons in the hippocampus after cerebral ischemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was observed in interneurons of the hippocampal CA1 sector. Furthermore, a significant decrease of PV immunoreactivity was found in interneurons of the hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1 sector up to 14 days after ischemia. Pitavastatin significantly prevented the neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our immunohistochemical study also showed that pitavastatin prevented significant decrease of PV-and nNOS-positive interneurons in the hippocampus after ischemia. Double-labeled immunostainings showed that PV immunoreactivity was not found in nNOS-immunopositive interneurons of the brain. The present study demonstrates that cerebral ischemia can cause a loss of both PV-and nNOS-immunoreactive interneurons in the hippocampal CA1 sector. Our findings also show that the damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our present study indicates that pitavastatin can prevent the damage of interneurons in the hippocampus after cerebral ischemia. Thus, our study provides valuable information for the pathogenesis after cerebral ischemia.