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Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation

Citation

Gerlai, R and McNamara, A and Choi-Lundberg, DL and Armanini, M and Ross, J and Powell-Braxton, L and Phillips, HS, Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation, European Journal of Neuroscience, 14, (7) pp. 1153-1163. ISSN 0953-816X (2001) [Refereed Article]

DOI: doi:10.1046/j.0953-816x.2001.01724.x

Abstract

Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Choi-Lundberg, DL (Dr Derek Choi-Lundberg)
ID Code:31415
Year Published:2001
Web of Science® Times Cited:72
Deposited By:Anatomy and Physiology
Deposited On:2005-03-03
Last Modified:2011-08-03
Downloads:0

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