Experimental modeling of functional deficiency of the nigrostriatal dopaminergic system in mice

: The dopaminergic nigrostriatal system is a key component of regulation of the motor behaviour. Cell bodies of dopaminergic DA-ergic neurons are located in the compact zone of the substantia nigra, and their axons are projected along the nigrostriatal tract to the striatum. This study was aimed to develop an experimental model of the functional insufficiency of the DA-ergic neurons of the nigrostriatal system without any manifestation of movement disorders, i.e., a model of presymptomatic stage of parkinsonism. This model has been developed with a single subcutaneous injection of a low dose of MPTP (12 mg/kg) which is converted in the brain into the MPP+, a neurotoxin of DA-ergic neurons. It has been shown that the MPTP injection on the 14th day is followed by: (a) absence of any sign of movement disorders; (b) no change in the DA content and the number of DA-ergic neurons in the substantia nigra; (c) substantial loss of DA in the striatum as a result of the degeneration of about 50% of DA-ergic axons. The absence of movement disorders under the substantial DA depletion and degradation of DA-ergic axons in the striatum is supposed to be a consequence of the turning on of the compensatory processes in the brain. Thus, we have developed the experimental model of presymptomatic stage of parkinsonism which is characterized by the degeneration of DA-ergic axons in the striatum without degradation of the neuron cell bodes in the substantia nigra.