Source Paper
Brain-Derived Neurotrophic Factor Regulates the Onset and Severity of Motor Dysfunction Associated with Enkephalinergic Neuronal Degeneration in Huntington's Disease
Josep M. Canals, José R. Pineda, Jesús F. Torres-Peraza, Miquel Bosch, Raquel Martín-Ibañez et al.
Journal of Neuroscience • 2004
BDNF Administration Study
Objective: To test restoration of striatal enkephalinergic neuronal dysfunction through exogenous BDNF administration in a transgenic mouse model of Huntington's disease
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Materials1
Not specified • Not specified • Not specified • Not specified
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Protocol Steps
Generate double mutant mouse line
Cross-mate bdnf +/- mice with R6/1 transgenic mice to create transgenic mice with mutant Huntingtin and different levels of BDNF
Note: This creates a model to compare transgenic mice for mutant Huntingtin with different levels of BDNF
View evidence from paper
“we disrupted the expression of bdnf in a transgenic mouse model by cross-mating bdnf +/- mice with R6/1 mice”
Assess motor dysfunction onset and severity
Monitor and evaluate motor dysfunctions in the double mutant mice to determine if decreased BDNF levels advance the onset and increase severity of uncoordinated movements
Note: Behavioral pathology correlates with loss of striatal dopamine and cAMP-regulated phosphoprotein-32-positive projection neurons
View evidence from paper
“The decreased levels of this neurotrophin advance the onset of motor dysfunctions and produce more severe uncoordinated movements”
Administer exogenous BDNF
Administer exogenous BDNF to mice with insufficient endogenous BDNF levels to test restoration of striatal enkephalinergic neuronal dysfunction
Note: Route of administration, dosage, and frequency not specified in provided text
View evidence from paper
“This neuronal dysfunction can specifically be restored by administration of exogenous BDNF”
Evaluate neuronal degeneration patterns
Assess specific degeneration of enkephalinergic striatal projection neurons and loss of dopamine and cAMP-regulated phosphoprotein-32-positive projection neurons
Note: Enkephalinergic striatal projection neurons are the most affected cells in Huntington's disease
View evidence from paper
“the insufficient levels of BDNF cause specific degeneration of the enkephalinergic striatal projection neurons, which are the most affected cells in Huntington's disease”