Dopamine Release in the Substantia Nigra and Striatum at Presymptomatic and Early Symptomatic Stages in Parkinsonian Mice

摘要

The degeneration of dopaminergic (DA-ergic) neurons of the nigrostriatal system results in the development of Parkinson's disease (PD). It is assumed that the increase of DA release from survived DA-ergic neurons might be one of the compensatory processes serving to maintain the DA concentration in the extracellular space at a normal level and thereby providing a long-lasting period of asymptomatic development of the disease. The goal of this study was to estimate DA release in the substantia nigra (SN) containing somas of DA-ergic neurons and in the striatum containing their axonal terminals under the different extents of the degradation of the nigrostriatal system corresponding to either presymptomatic or symptomatic stage of parkinsonism in mice. In the ex vivo studies of the brain slices under perfusion, it has been shown that the values of both spontaneous and K~+-stimulated release of DA in the SN at both stages of parkinsonism were the same as those in the controls suggesting the increase of DA release from the survived somas of DA-ergic neurons. In the striatum at presymptomatic and symptomatic stages, no compensatory modification of spontaneous DA release was observed whereas K~+-stimulated release of DA from the survived axonal terminals increased significantly. However, the total amount of DA released at symptomatic stage was below the control level that was in contrast to that at presymptomatic stage. This observation is probably among the reasons of the appearance of the initial symptoms of parkinsonism.