Ermine C, Wright JL, Parish CL, Thompson LH (2015) Direct impact of dopaminergic and noradrenergic systems on adult-hippocampal neurogenesis in adult rats and the relevance to dementia in Parkinson’s disease. Neuroscience 2015 Abstracts 217.06/C66. Society for Neuroscience, Chicago IL.
Summary: A key pathological feature of Parkinson’s disease (PD) is the progressive degeneration of midbrain dopaminergic neurons, causing motor dysfunction. However there are a range of ‘non-movement’ related features (including cognitive dysfunction, dementia and sleep disorder), which are not alleviated by dopamine replacement therapy. We are currently investigating the hypothesis that reduced hippocampal neurogenesis contributes to cognitive dysfunction in PD. We aim to characterise the effect of the dopaminergic and noradrenergic system on the adult-hippocampal neurogenesis in order to identify potential targets for the treatment cognitive impairments related to neurogenesis. We induced lesions of the different systems in adult rats using stereotaxic injections of toxins: 6-hydroxydopamine (dopaminergic system) and anti-dopa-β-hydroxylase-saporin (noradrenergic system). Four weeks later, the new cells were marked by pulses of bromodeoxyuridine (Brd-U) twice daily for 1 week. The animals were then sacrificed 4 weeks later for tissue collection. A high-performance liquid chromatography has confirmed that both lesions were successful: dopamine level in the striatum dropped to 20% and noradrenaline level in the hippocampus dropped to 8.3%. Surprisingly there was no difference in the number of Brd-U positive cells or in the number of double positive Brd-U/NeuN cells between our groups. The results show that while both noradrenergic and dopaminergic systems are implicated in the onsets of non-motor symptoms, they may not act through the regulation of adult-hippocampal neurogenesis like it was previously thought. Importantly our project has allowed reconsideration of how neurogenesis is involved in PD and redirected the therapies to better potential targets for treatment.
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