title: Age-related gene expression changes in substantia nigra dopamine neurons of the rat.
abstract: Ageing affects most, if not all, functional systems in the body. For example, the somatic motor nervous system, responsible for initiating and regulating motor output to skeletal musculature, is vulnerable to ageing. The nigrostriatal dopamine pathway is one component of this system, with deficits in dopamine signalling contributing to major motor dysfunction, as exemplified in Parkinson's disease (PD). However, while the dopamine deficit in PD is due to degeneration of substantia nigra (SN) dopamine (DA) neurons, it is unclear whether there is sufficient loss of SN DA neurons with ageing to explain observed motor impairments. Instead, evidence suggests that age-related loss of DA neuron function may be more important than frank cell loss. To further elucidate the mechanisms of functional decline, we have investigated age-related changes in gene expression specifically in laser microdissected SN DA neurons. There were significant age-related changes in the expression of genes associated with neurotrophic factor signalling and the regulation of tyrosine hydroxylase activity. Furthermore, reduced expression of the DA neuron-associated transcription factor, Nurr1, may contribute to these changes. Together, these results suggest that altered neurotrophic signalling and tyrosine hydroxylase activity may contribute to altered DA neuron signalling and motor nervous system regulation in ageing.
authors.affiliation: Preclinical Neurobiology Research Program, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1/Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia. Electronic address: gemma.parkinson@uon.edu.au.
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Parkinson
authors.affiliation: Preclinical Neurobiology Research Program, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1/Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia. Electronic address: christopher.dayas@newcastle.edu.au.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Dayas
authors.affiliation: Preclinical Neurobiology Research Program, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, 1/Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia. Electronic address: douglas.smith@newcastle.edu.au.
authors.forename: Doug W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D000375:Aging; D000818:Animals; D002470:Cell Survival; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006136:GTP Cyclohydrolase / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D007834:Lasers; D008297:Male; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D020813:Receptor, trkB / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology*; D013997:Time Factors
chemical_list: D017931:DNA Primers; C494989:Gfra1 protein, rat; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D020813:Receptor, trkB; D006136:GTP Cyclohydrolase; D004298:Dopamine
keywords: Ageing; Dopamine neuron; Gene expression; Laser microdissection; Substantia nigra