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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/33017
Title: Brain-derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease
Authors: Adell, Albert; Mengod Los Arcos, Guadalupe ; Artigas, Francesc ; Alberch, Jordi
Keywords: Amphetamine
Axonal transport
Movement disorders
Neuronal dysfunction
Substantia nigra
Issue Date: Jun-2005
Publisher: Wiley-Blackwell
Citation: Journal of Neurochemistry 93(5): 1057–1068 (2005)
Abstract: Dysfunction of dopaminergic neurons may contribute to motor impairment in Huntington's disease. Here, we study the role of brain-derived neurotrophic factor (BDNF) in alterations of the nigrostriatal system associated with transgenics carrying mutant huntingtin. Using huntingtin-BDNF+/– double-mutant mice, we analyzed the effects of reducing the levels of BDNF expression in a model of Huntington's disease (R6/1). When compared with R6/1 mice, these mice exhibit an increased number of aggregates in the substantia nigra pars compacta. In addition, reduction of BDNF expression exacerbates the dopaminergic neuronal dysfunction seen in mutant huntingtin mice, such as the decrease in retrograde labelling of dopaminergic neurons and striatal dopamine content. However, mutant huntingtin mice with normal or lowered BDNF expression show the same decrease in the anterograde transport, number of dopaminergic neurons and nigral volume. In addition, reduced BDNF expression causes decreased dopamine receptor expression in mutant huntingtin mice. Examination of changes in locomotor activity induced by dopamine receptor agonists revealed that, in comparison with R6/1 mice, the double mutant mice exhibit lower activity in response to amphetamine, but not to apomorphine. In conclusion, these findings demonstrate that the decreased BDNF expression observed in Huntington's disease exacerbates dopaminergic neuronal dysfunction, which may participate in the motor disturbances associated with this neurodegenerative disorder.
Publisher version (URL): http://dx.doi.org/10.1111/j.1471-4159.2005.03047.x
URI: http://hdl.handle.net/10261/33017
DOI: 10.1111/j.1471-4159.2005.03047.x
ISSN: 0022-3042
E-ISSN: 1471-4159
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