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).
Cite this paper
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.
 Nussbaum, R.L. and Polymeropoulos, M.H. (1997) Genetics of Parkinson’s disease. Human Molecular Genetics, 6, 1687-1691. doi:10.1093/hmg/6.10.1687
 Shadrina, M.I., Slominsky, P.A. and Limborska, S.A. (2010) Molecular mechanisms of pathogenesis of Parkinson’s disease. International Review of Cell & Molecular Biology, 281, 229-266.
 Saiki, S., Sato, S. and Hattori, N. (2012) Molecular pathogenesis of Parkinson’s disease: Update. Journal of Neurology, Neurosurgery & Psychiatry, 83, 430-436.
 Blandini, F. and Armentero, M.T. (2012) Animal models of Parkinson’s disease. FEBS Journal, 279, 1156-1166.
 Ungerstedt, U., Ljungberg, T. and Steg, G. (1974) Behavioral, physiological, and neurochemical changes after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons. Advances in Neurology, 5, 421-426.
 Sauer, H. and Oertel, W.H. (1994) Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: A combined retrograde tracing and immunocytochemical study in the rat. Neuroscience, 59, 401-415.
 Blandini, F., Armentero, M.T. and Martignoni, E. (2008) The 6-hydroxydopamine model: News from the past. Parkinsonism & Related Disorders, 14, S124-129.
 Chen, X.Y., Li, J., Qi, W.Q. and Shen, S.H. (2007) Experimental change on dopaminergic neurons in striatum of Parkinson disease rats. Histology and Histopathology, 22, 1085-1090.
 Urbanavicius, J., Ferreira, M., Costa, G., Abin-Carriquiry, J.A., Wonnacott, S., et al. (2007) Nicotine induces tyrosine hydroxylase plasticity in the neurodegenerating striatum. Journal of Neurochemistry, 102, 723-730.
 Huang da, W., Sherman, B.T., and Lempicki, R.A. (2009) Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Research, 37, 1-13. doi:10.1093/nar/gkn923
 Huang da, W., Sherman, B.T. and Lempicki, R.A. (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols, 4, 44-57. doi:10.1038/nprot.2008.211
 Caldwell, H.K., Lee, H.J., Macbeth, A.H. and Young, W.S. (2008) Vasopressin: Behavioral roles of an “original” neuropeptide. Progress in Neurobiology, 84, 1-24.
 Orr, C.F., Rowe, D.B. and Halliday, G.M. (2002) An inflammatory review of Parkinson’s disease. Progress in Neurobiology, 68, 325-340.
 Na, S.J., DiLella, A.G., Lis, E.V., Jones, K., Levine, D.M., et al. (2010) Molecular profiling of a 6-hydroxydopamine model of Parkinson’s disease. Neurochemical Research, 35, 761-772. doi:10.1007/s11064-010-0133-3
 Mitchell, J.D., Maguire, J.J. and Davenport, A.P. (2009) Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S. British Journal of Pharmacology, 158, 87-103.
 Ohno, K., Saito, S., Sugawara, K., Suzuki, T., Togawa, T., et al. (2009) Structural basis of neuronal ceroid lipofuscinosis 1. Brain & Development, 32, 524-530.
 Zhang, L., Sheng, R. and Qin, Z. (2009) The lysosome and neurodegenerative diseases. Acta Biochimica et Biophysica Sinica, 41, 437-445. doi:10.1093/abbs/gmp031
 Guergueltcheva, V., Azmanov, D.N., Angelicheva, D., Smith, K.R., Chamova, T., et al. (2012) Autosomal-recessive congenital cerebellar ataxia is caused by mutations in metabotropic glutamate receptor 1. The American Journal of Human Genetics, 91, 553-564.
 Imai, Y. and Lu, B. (2011) Mitochondrial dynamics and mitophagy in Parkinson’s disease: Disordered cellular power plant becomes a big deal in a major movement disorder. Current Opinion in Neurobiology, 21, 935-941.
 Soos, J., Engelhardt, J.I., Siklos, L., Havas, L. and Majtenyi, K. (2004) The expression of PARP, NF-kappa B and parvalbumin is increased in Parkinson disease. Neuroreport, 15, 1715-1718.
 Ugrumov, M.V., Khaindrava, V.G., Kozina, E.A., Kucheryanu, V.G., Bocharov, E.V., et al. (2011) Modeling of presymptomatic and symptomatic stages of parkinsonism in mice. Neuroscience, 181, 175-188.