title: Nigrostriatal interaction in the aging brain: new therapeutic target for Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder of unclear etiology and pathogenesis. Research results gathered to date support the hypothesis that the motor symptoms of the disease result from the gradual loss of midbrain dopamine neurons residing in the substantia nigra pars compacta (SNpc). Recent discoveries, however, significantly expand this knowledge indicating that the primary source of the PD pathogenesis may be located both in the SNpc as well as in the GABAergic striatum. Newly discovered striatal neurogenesis - normally a lifelong process - determines the efficiency of nigrostriatal interaction. Deficient neurogenesis within the striatum followed by a decline in the GABAergic/dopaminergic interaction results in progressive disconnection of the dopaminergic input, which initiates a 'vicious circle' cascade of neuronal damage. Effects of both deficient striatal neurogenesis and age-related neurodegeneration within the striatum accumulate, resulting in a progressive decline in the control functions of the basal ganglia, loss of dopaminergic neurons, and occurrence of PD clinical symptoms. Functional and pharmacological control of these dynamic relationships may result in treatments that are more effective with fewer side-effects.
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology, Warsaw, Poland, and Jerzy Kukuczka Academy of Physical Education, Katowice, Poland, j.blaszczyk@nencki.gov.pl.
authors.forename: Janusz W
authors.initials: JW
authors.lastname: Błaszczyk
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D003342:Corpus Striatum / Q000473:pathology*; D006801:Humans; D009410:Nerve Degeneration / Q000150:complications* / Q000473:pathology; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology / Q000628:therapy; D013378:Substantia Nigra / Q000473:pathology*