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
Transgenic Mouse Behavioral Analysis
Objective: Analyze motor dysfunction onset and severity in double mutant mice (R6/1 with bdnf +/- background) to determine how BDNF levels modulate Huntington's disease pathology and motor phenotype
Protocol Steps
Generate double mutant mouse lines
Cross-mate bdnf +/- mice with R6/1 transgenic mice to create transgenic mice with mutant Huntingtin and different levels of BDNF expression
Note: This creates a model to compare the effects of different BDNF levels on Huntington's disease pathology
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
Monitor and record the onset of motor dysfunctions in the double mutant mice with different BDNF levels
Note: Specific behavioral testing methods not detailed in provided text
View evidence from paper
“The decreased levels of this neurotrophin advance the onset of motor dysfunctions and produce more severe uncoordinated movements”
Evaluate motor dysfunction severity
Measure the severity of uncoordinated movements and motor deficits in transgenic mice with different BDNF levels
Note: Behavioral pathology correlates with striatal neuronal loss
View evidence from paper
“This behavioral pathology correlates with the loss of striatal dopamine and cAMP-regulated phosphoprotein-32-positive projection neurons”
Analyze striatal neuronal pathology
Examine loss of striatal dopamine and cAMP-regulated phosphoprotein-32-positive projection neurons, with particular focus on enkephalinergic striatal projection neurons
Note: Enkephalinergic 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”
Test BDNF rescue effects
Administer exogenous BDNF and assess whether it restores neuronal dysfunction and motor phenotype
Note: Exogenous BDNF specifically restores enkephalinergic neuronal dysfunction
View evidence from paper
“This neuronal dysfunction can specifically be restored by administration of exogenous BDNF”