Age-related gene expression changes in substantia nigra dopamine neurons of the rat. (July 2015)

• Record Type: Journal Article
• Authors: Parkinson, Gemma M.; Dayas, Christopher V.; Smith, Doug W.
• Is Part Of: Mechanisms of ageing and development. Volume 149(2015)
• Page Start: 41
• Page End: 49
• Publication Date: 2015-07
• Subjects: Substantia nigra -- Laser microdissection -- Dopamine neuron -- Gene expression -- Ageing; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2015.06.002
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: Gene expression in laser microdissected rat SN DA neurons is altered by ageing. Alteration of neurotrophic factor receptor gene expression occurs with age. Neuronal transcription factor Nurr1 expression is reduced with age. 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.