WEDNESDAY, Feb. 20 (HealthDay News) -- High levels of monoamine oxidase B (MAO-B) caused Parkinson's disease-like symptoms in a novel transgenic mouse model genetically engineered to overexpress the enzyme, according to research published online Feb. 20 in PLoS One. These results may provide a new model for exploring diagnostic options and allow for additional therapeutic drug testing, the study authors note.
Jyothi K. Mallajosyula, of the Buck Institute for Age Research in Novato, Calif., and colleagues created genetically engineered transgenic mouse lines in which astroglial MAO-B levels could be specifically induced in the adult animals.
The researchers found that elevation in astrocytic MAO-B activity resulted in a specific, selective and progressive loss of dopaminergic neurons in the substantia nigra in an age-dependent manner. Additional Parkinson-associated manifestations were also seen, including selective decreases in mitochondrial complex I activity, increased levels of mitochondrial oxidative stress, and local microglial activation within the substantia nigra. These manifestations were associated with decreased locomotor activity and occurred even in the absence of administration of the Parkinson-inducing neurotoxin MPTP.
"Our inducible astrocytic MAO-B transgenic line provides a novel model for exploring pathways involved in initiation or early progression of several key features associated with Parkinson's disease pathology and for therapeutic drug testing," the authors write.
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