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Age-related gene expression changes in substantia nigra dopamine neurons of the rat
- Source :
- Mechanisms of ageing and development. 149
- Publication Year :
- 2014
-
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.
- Subjects :
- Male
medicine.medical_specialty
Aging
Glial Cell Line-Derived Neurotrophic Factor Receptors
Time Factors
Cell Survival
Dopamine
Substantia nigra
Biology
Neurotrophic factors
Internal medicine
Motor system
Gene expression
Nuclear Receptor Subfamily 4, Group A, Member 2
medicine
Animals
Receptor, trkB
GTP Cyclohydrolase
DNA Primers
Dopaminergic Neurons
Gene Expression Profiling
Lasers
Rats, Inbred F344
Rats
Substantia Nigra
Endocrinology
medicine.anatomical_structure
Phenotype
Gene Expression Regulation
Ageing
biology.protein
Neuron
Neuroscience
Developmental Biology
medicine.drug
Neurotrophin
Subjects
Details
- ISSN :
- 18726216
- Volume :
- 149
- Database :
- OpenAIRE
- Journal :
- Mechanisms of ageing and development
- Accession number :
- edsair.doi.dedup.....adfc2f6e75e4c6074f6105e76151d663