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Cognitive deficits in animal models of basal ganglia disorders

Brooks, Simon Philip and Dunnett, Stephen Bruce 2013. Cognitive deficits in animal models of basal ganglia disorders. Brain Research Bulletin 92 , pp. 29-40. 10.1016/j.brainresbull.2012.04.011

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Abstract

The two most common neurological disorders of the basal ganglia are Parkinson's disease (PD) and Huntington's disease (HD). The most overt symptoms of these diseases are motoric, reflecting the loss of the striatal medium spiny neurons in HD and ascending substantia nigra dopaminergic cells in PD. However, both disease processes induce insidious psychiatric and cognitive syndromes that can manifest well in advance of the onset of motor deficits. These early deficits provide an opportunity for prophylactic therapeutic intervention in order to retard disease progression from the earliest possible point. In order to exploit this opportunity, animal models of HD and PD are being probed for the specific cognitive deficits represented in the disease states. At the neuronal level, these deficits are typically, but not exclusively, mediated by disruption of parallel corticostriatal loops that integrate motor information with sensory and higher order, “executive” cognitive functions. Dysfunction in these systems can be probed with sensitive behavioural tests that selectively probe these cognitive functions in mouse models with focal lesions of striatal or cortical regions, or of specific neurotransmitter systems. Typically these tests were designed and validated in rats. With the advent of genetically modified mouse models of disease, validated tests provide an opportunity to screen mouse models of disease for early onset cognitive deficits. This review seeks to draw together the literature on cognitive deficits in HD and PD, to determine the extent to which these deficits are represented in the current animal models of disease, and to evaluate the viability of selecting cognitive deficits as potential therapeutic targets.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Huntington's disease; Parkinson's disease; Cognition; Review; 6-OHDA; MPTP; Behaviour; Phenotype; Cognitive tests; Basal ganglia; Corticostriatal; Dopamine
Additional Information: This article is part of a Special Issue entitled ‘Animal Models’.
Publisher: Elsevier
ISSN: 0361-9230
Last Modified: 04 Jun 2017 04:37
URI: http://orca.cf.ac.uk/id/eprint/41695

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