Neurokinin receptor 3 peptide exacerbates 6-hydroxydopamine-induced dopaminergic degeneration in rats through JNK pathway
Article first published online: 10 SEP 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 3, pages 417–427, November 2012
How to Cite
Chu, J. M. T., Chan, Y. S., Chen, L. W. and Yung, K. K. L. (2012), Neurokinin receptor 3 peptide exacerbates 6-hydroxydopamine-induced dopaminergic degeneration in rats through JNK pathway. Journal of Neurochemistry, 123: 417–427. doi: 10.1111/j.1471-4159.2012.07858.x
- Issue published online: 8 OCT 2012
- Article first published online: 10 SEP 2012
- Accepted manuscript online: 4 JUL 2012 02:40PM EST
- Received May 23, 2012; revised manuscript received June 24, 2012; accepted June 30, 2012.
- dopaminergic degeneration;
- dopaminergic neurons;
- neurokinin 3 receptor
J. Neurochem. (2012) 123, 417–427.
Neurokinin 3 (NK3) receptor is predominantly expressed in striatum and substantia nigra (SN). Evidences have indicated the roles of NK3 receptor in the pathogenesis of Parkinson’s disease. By administrating NK3 receptor agonist senktide into 6-hydroxydopamine (6-OHDA)-lesioned rats, exacerbation of dopaminergic degeneration was found in striatum and substantia nigra pars compacta. From apomorphine rotation test, significant increase of contralateral rotation number was detected in 6-OHDA-lesioned rats with senktide injection. Furthermore, tyrosine hydroxylase expression in striatum and substantia nigra pars compacta were examined by immunohistochemistry and Western blotting. Further reduction of tyrosine hydroxylase immunoreactivities was found in 6-OHDA-lesioned rats that received senktide treatment. Also, phosphorylation of N-methyl-D-aspartate receptor 1 subunit was investigated in SN region and significant up-regulation was revealed in senktide-treated 6-OHDA-lesioned rats. Finally, phosphorylation of mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and c-Jun were examined in nigral region. Up-regulation of phosphorylated JNK molecules was shown in SN region after senktide injection. In line with this evidence, phosphorylation of c-Jun at Ser 63 and Ser 73 was also up-regulated by senktide treatment, thus presenting new aspects that NK3 peptide could exacerbate 6-OHDA toxicity in in vivo models and the possible mechanism may be contributed by the modulation of N-methyl-D-aspartate receptor 1 subunit and JNK pathway activities.