ABSTRACT
Analysis
of monogenic forms and candidate genes of Parkinson’s disease (PD) does not
allow to describe completely the contribution of genetic factors to the
etiopathogenesis of the disorder. An approach associated with an analysis of
changes in a transcriptome pattern during the development of the disease in
model objects can be used to identify new candidate genes that are involved in
the pathogenesis of PD. In this work, we performed a transcriptome analysis of
a PD model, created via stereotaxic unilateral introduction of the
6-hydroxidopamine (6-OHDA) into the substantia nigra pars compacta (SNpc) of a
rat brain, to identify new candidate genes for PD. We studied transcriptome alterations
in the substantia nigra of the rat brains 2 weeks after toxin administration,
when the rats developed the Parkinson-like phenotype, and 4 weeks after toxin
administration, when maximal changes in the behavior of animals were observed.
The transcriptome analysis of the substantia nigra of the rat brains at the
first time point (2 weeks) revealed changes in expression of genes that were
clustered with high significance (p < 0.01, modified Fisher extract p
value) into three metabolic pathways according to protein participation: modification of the extracellular matrix, signal transduction (including genes
encoding signal peptides), and inflammation processes. This likely indicates
that, during this time nonspecific effects associated with the response to
surgery took place in the substantia nigra of the rats. Concomitantly, the
situation changed dramatically and a response associated with damage to the
nervous tissue was observed 4 weeks after neurotoxin administration. As a
result, we identified five metabolic pathways containing predominantly genes,
that encode protein products that are involved in the processes of neuron
projection, normal functioning of the soma and dendrites of neurons, synaptic
transmission, and transmission of nerve impulses (p < 0.01, modified
Fisher extract p value).
Share and Cite:
Shadrina, M. , Filatova, E. , Alieva, A. , Stavrovskaya, A. , Khudoerkov, R. , Limborska, S. , Illarioshkin, S. and Slominsky, P. (2013) Transcriptome profiling of 6-OHDA model of Parkinson’s disease.
Advances in Bioscience and Biotechnology,
4, 28-35. doi:
10.4236/abb.2013.46A005.