Abstract
We have previously shown that increases in astrocytic monoamine oxidase-B (MAO-B) expression, mimicking that which occurs with aging and in neurodegenerative disease, in a doxycycline (dox)-inducible transgenic mouse model evokes neuropathological similarities to what is observed in the human parkinsonian brain. Additional behavioral and neuropathological studies could provide further validation for its usage as a model for Parkinson’s disease (PD). In the present study, we utilized a battery of behavioral tests to evaluate age-related phenotype in this model. In the open field test, we found that dox-induction impaired motor ability with decreases in movement and ambulatory function as well as diminished stereotypical, repetitive movement episodes in both young and old mice. Older mice also showed decreased motor performance in the pole test when compared to younger mice. Furthermore, dox-induced older mice displayed severe hindlimb clasping and the most significant loss of dopamine (DA) in the striatum when compared to young and non-induced animals. Additionally, increased MAO-B activity significantly correlated with decreased expression of striatal DA. The results of our study further confirms that the dox-inducible astrocytic MAO-B transgenic mouse displays similar age-related behavioral and neuropathological features to other models of PD, and could serve as a useful tool to study PD pathophysiology and for the evaluation of therapeutic interventions.
Highlights
Parkinson’s disease (PD) is a common, neurodegenerative disorder characterized by bradykinesia, muscle rigidity, postural instability and resting tremor
Monoamine oxidase-B (MAO-B) is an enzyme found in astrocytes and has been implicated in the neurodegenerative process associated with aging and in neurodegenerative diseases including Parkinson’s and Alzheimer’s disease [1]
Age-related increases in MAO-B expression is associated with increases in free radical damage and reactive oxygen species (ROS) [2,3,4,5]
Summary
Parkinson’s disease (PD) is a common, neurodegenerative disorder characterized by bradykinesia (slowness of movement), muscle rigidity, postural instability and resting tremor. Age-related increases in MAO-B expression is associated with increases in free radical damage and reactive oxygen species (ROS) [2,3,4,5]. This increase in free radicals and ROS via age-related increases in MAO-B expression has been reported to lead to decreases in neuronal mitochondrial function, deterioration of substantia nigra dopaminergic neuron viability, and leads to cell death [6,7] and motor impairment. It is evident that MAO-B plays an important role in the progressive nature of neurodegenerative diseases and subsequent behavioral pathophysiology
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