PMID- 11683907
DA - 20011030
DCOM- 20011207
IS - 0953-816X
VI - 14
IP - 7
DP - 2001 Oct
TI - Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation.
PG - 1153-63 AB - 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.
AD - Department of Neuroscience, Genentech Inc, 1 DNA Way, South San Francisco,
[emd]
FAU - Gerlai, R
AU - Gerlai R
FAU - McNamara, A
AU - McNamara A
FAU - Choi-Lundberg, D L
AU - Choi-Lundberg DL
FAU - Armanini, M
AU - Armanini M
FAU - Ross, J
AU - Ross J
FAU - Powell-Braxton, L
AU - Powell-Braxton L
FAU - Phillips, H S
AU - Phillips HS
LA - eng
PT - Journal Article
CY - France
TA - Eur J Neurosci
JID - 8918110
RN - 0 (Nerve Tissue Proteins)
RN - 0 (glial cell-line derived neurotrophic factor)
RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN - 51-61-6 (Dopamine)
SB - IM
MH - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH - Animal
MH - Brain/*metabolism/physiopathology
MH - Dopamine/*metabolism
MH - Gene Expression/genetics
MH - *Heterozygote
MH - Learning Disorders/*genetics/metabolism/physiopathology
MH - Maze Learning/*physiology
MH - Mice
MH - Mice, Knockout
MH - Motor Activity/genetics
MH - Mutation/*physiology
MH - Neostriatum/metabolism/physiopathology
MH - Nerve Tissue Proteins/*deficiency/genetics
MH - Neural Pathways/metabolism/physiopathology
MH - Organ Weight/genetics
MH - Substantia Nigra/metabolism/physiopathology
EDAT- 2001/10/31 10:00
MHDA- 2002/01/05 10:01
AID - 1724 [pii]
PST - ppublish
SO - Eur J Neurosci 2001 Oct;14(7):1153-63.