dc.contributor.author |
McGregor, Ailsa |
en |
dc.contributor.author |
D'Souza, G |
en |
dc.contributor.author |
Kim, Donghyo |
en |
dc.contributor.author |
Tingle, Malcolm |
en |
dc.date.accessioned |
2017-04-06T04:05:52Z |
en |
dc.date.issued |
2017-04 |
en |
dc.identifier.citation |
Neuropharmacology 116:233-246 Apr 2017 |
en |
dc.identifier.issn |
0028-3908 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/32485 |
en |
dc.description.abstract |
Objective Studies in the post mortem human brain and in genetic mouse model suggest that dysfunctional cholinergic neurotransmission, through a loss of agonist rather than receptors may be a significant contributing factor to HD pathology. If correct, pharmacological replacement may therefore be a potential treatment strategy. We have investigated whether chronic administration of the selective nicotinic partial agonist varenicline improved motor, cognitive and affective symptoms in a transgenic mouse model of Huntington's disease. Method The performance of 15 month old YAC128 mice and age-matched wild-type littermates was assessed in the rotarod, T-maze, novel object recognition, novelty suppressed feeding and forced swim tests prior to and after treatment with varenicline (5 mg/kg/day for 28 days via miniosmotic pump). Thymidine analogues, whilst DARPP32 and EM48 immunohistochemistry were used to assess the effect of varenicline on progenitor cell proliferation and survival, medium spiny neurons and aggregate formation respectively. Results Chronic treatment with varenicline significantly improved motor coordination, delay-dependent memory and reduced depressive-like behaviour in late stage YAC128 mice. Varenicline also produced genotype-independent improvements in recognition memory and reduced anxiety. In addition, varenicline displayed anxiolytic effects and improved spatial memory in the absence of compromised function. Functional improvements were accompanied by neuropathological changes including increased aggregate formation, neuroprotection and increased progenitor cell proliferation and survival. Interpretation Our findings provide evidence that administration of an exogenous nicotinic agonist may be of clinical benefit in the treatment of late-stage Huntington's disease. |
en |
dc.publisher |
Pergamon Press Ltd. |
en |
dc.relation.ispartofseries |
Neuropharmacology |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0028-3908/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
en |
dc.title |
Varenicline improves motor and cognitive deficits and decreases depressive-like behaviour in late-stage YAC128 mice |
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dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.neuropharm.2016.12.021 |
en |
pubs.begin-page |
233 |
en |
pubs.volume |
116 |
en |
dc.description.version |
AM - Accepted Manuscript |
en |
dc.rights.holder |
Copyright: Elsevier |
en |
dc.identifier.pmid |
28025093 |
en |
pubs.end-page |
246 |
en |
pubs.publication-status |
Accepted |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
605544 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Pharmacology |
en |
pubs.record-created-at-source-date |
2017-04-06 |
en |
pubs.dimensions-id |
28025093 |
en |