Several studies have indicated that Parkinson’s disease (PD) is more common in males as opposed to females. PD results from degeneration of dopamine containing neurons in the midbrain. Flow of dopamine through the basal ganglia, striatum, and regions of the cerebral cortex is impaired. In addition, the dopamine output from the substantia nigra, located within the mesencephalon, is diminished. Results from a study comparing male and female mice found that female mice have a more active and efficient dopamine transporter system (DAT); the recovery and vesicular packaging of extracellular dopamine and clearance of dopamine from the synapse is more effective in female mice. These findings imply that female mice are less susceptible to the effects of neurotoxins which utilize the DAT to exert their effects. The neurotoxin 1-methyl-4-phenylpyridinium (MPP+) has been used in previous studies to mimic the effects of PD in nonhuman animals. MPP+, a selective toxin for dopaminergic neurons, severely damages these neurons contained in the substantia nigra similar to the way in which cell loss occurs in PD. Higher concentrations of MPP+ have been shown to have a more damaging effect on the synthesis of dopamine containing neurons. Areas of the brain containing dopaminergic neurons including the midbrain, frontal cortex, and the striatum were cultured from male and from female rat fetuses and treated with MPP+ to investigate whether male dopaminergic neurons would be more sensitive to the effects of MPP+ than female dopaminergic neurons. The effect of MPP+ on cultures prepared from male and female fetal brains was assessed by looking for the presence of a dopamine containing enzyme, tyrosine hydroxylase (TH). Positive stains for TH were found in neurons within the midbrain and striatal cultures. In previous studies TH positive cells have been found in the ventral portion of the striatum and the number of striatal TH positive neurons was shown to vary inversely with the age of the subjects. The difficulty in determining the sex of the 15 day gestation rat fetuses may have contributed to overall results which did not indicate more damage to male cultures as opposed to female cultures in response to treatment with MPP+.
Victoria Levasseur, ’11 Cedar Rapids, IA
Majors: Biochemistry and Molecular Biology, Spanish
Sponsor: Barbara Christie-Pope