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Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson's disease and the impact on hippocampal neurogenesis

Ermine, CM; Wright, JL; Frausin, S; Kauhausen, JA; Parish, CL; Stanic, D; Thompson, LH; (2018) Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson's disease and the impact on hippocampal neurogenesis. Hippocampus , 28 (5) pp. 327-337. 10.1002/hipo.22835. Green open access

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Abstract

Key pathological features of Parkinson's Disease (PD) include the progressive degeneration of midbrain dopaminergic (DA) neurons and hindbrain noradrenergic (NA) neurons. The loss of DA neurons has been extensively studied and is the main cause of motor dysfunction. Importantly, however, there are a range of ‘non‐movement’ related features of PD including cognitive dysfunction, sleep disturbances and mood disorders. The origins for these non‐motor symptoms are less clear, but a possible substrate for cognitive decline may be reduced adult‐hippocampal neurogenesis, which is reported to be impaired in PD. The mechanisms underlying reduced neurogenesis in PD are not well established. Here we tested the hypothesis that NA and DA depletion, as occurs in PD, impairs hippocampal neurogenesis. We used 6‐hydroxydopamine or the immunotoxin dopamine‐β‐hydroxylase‐saporin to selectively lesion DA or NA neurons, respectively, in adult Sprague Dawley rats and assessed hippocampal neurogenesis through phenotyping of cells birth‐dated using 5‐bromo‐2′‐deoxyuridine. The results showed no difference in proliferation or differentiation of newborn cells in the subgranular zone of the dentate gyrus after NA or DA lesions. This suggests that impairment of hippocampal neurogenesis in PD likely results from mechanisms independent of, or in addition to degeneration of DA and NA neurons.

Type: Article
Title: Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson's disease and the impact on hippocampal neurogenesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hipo.22835
Publisher version: https://doi.org/10.1002/hipo.22835
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. VC 2018 The Authors. Hippocampus Published by Wiley Periodicals, Inc. For Further info see here: https://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, catecholamines, dentate gyrus, endogenous stem-cells, neurodegeneration, NEURAL PRECURSOR CELLS, ADULT-RAT HIPPOCAMPUS, SUBVENTRICULAR ZONE, CATECHOLAMINE NEURONS, EFFERENT PROJECTIONS, ALZHEIMERS-DISEASE, LOCUS-CERULEUS, PROLIFERATION, BRAIN, DEPLETION
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10065969
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