Finding
Our investigations demonstrated that a deficiency of the dopaminergic nigrostriatal system causes destruction of inhibitor neurons in the caudate nuclei.
Paper
Mechanisms of parkinsonism
Abstract
Professor Georgy Kryzhanovsky L a b o r a t o r y investigation has resulted in new approaches to elucidating the pathogenesis of parkinsonism. We used microelectrode recordings to help determine some of t h e mechanisms of neuronal degeneration as related to specific neurochemical profiles. Our investigations demonstrated that a deficiency of the dopaminergic nigrostriatal system causes destruction of inhibitor neurons in the caudate nuclei. Depression and hyperactivation of neurons in the striatum results in the formation of a generator of pathologically enhanced excitation (GPE El. GPEEs form the pathophysiologic basis for clinical symptoms of parkinsonism, including akinesia, rigidity, and tremor. These symptoms of parkinsonism can be induced by injecting the neurotoxin 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) or its metabolite, l-methyl-4-phenyl-pyridinium (MPP+), into the substantia nigra and destroying presynaptic dopaminergic neurons. Endogenous, physiologically active substances such as neurotransmitters and peptides may modulate the level of activity of GPEEs, causing parkinsonism. Enhanced excitation in the caudate nuclei also can be induced by introducing cholinomimetics. GPEEs are sup-
Authors
G. Kryzhanovsky
Journal
Neurology