Document Type

Journal Article

Department/Unit

Department of Biology

Title

Neurokinin receptor 3 peptide exacerbates 6-hydroxydopamine-induced dopaminergic degeneration in rats through JNK pathway

Language

English

Abstract

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. Neurokinin receptor 3 (NK3R) is colocalized with dopaminergic neurons, but the roles of this receptor in Parkinson's disease are still unclear. Administration of NK3 peptide senktide into 6-OHDA-lesioned rats resulted in exacerbation of dopaminergic degeneration, activation of NR1 and JNK pathway. Our data indicated that NK3R may involve in the onset of PD progress and subsequent neuronal degeneration. © 2012 International Society for Neurochemistry.

Keywords

6-OHDA, dopaminergic degeneration, dopaminergic neurons, JNK, neurokinin, neurokinin 3 receptor

Publication Date

2012

Source Publication Title

Journal of Neurochemistry

Volume

123

Issue

3

Start Page

417

End Page

427

Publisher

Wiley

DOI

10.1111/j.1471-4159.2012.07858.x

ISSN (print)

00223042

ISSN (electronic)

14714159

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