Protection Against Nigrostriatal Dopamine Cell Death by Pedunculopontine Tegmental Nucleus Lesions
It is well known that the pathogenesis of Parkinson’s disease is striatal dopamine deficiency subsequent upon degeneration of neurons in the substantia nigra pars compacta (SNc, Albin et al., 1989; DeLong, 1990). Several lines of evidence indicate that the pedunculopontine tegmental nucleus (PPN) is a major origin of excitatory glutamatergic input to nigrostriatal dopamine neurons (Kojima et al., 1997; Scarnati and Florio, 1997; Bezard and Gross, 1998). Recently, the importance of enhanced glutamatergic neurotransmission in the basal ganglia and related structures has been emphasized in the development of Parkinson’s disease (Greenamyre, 1993; Schmidt, 1995; Starr, 1995; Lange et al., 1997). Based on the previous idea that an excitatory mechanism mediated by glutamatergic neurotransmission is closely associated with the onset of neurodegenerative disorders (Choi, 1988; Olney, 1988, 1989; Klockgether and Turski, 1989), we tested the hypothesis that ablation of the glutamatergic input derived from the PPN might prevent nigrostriatal cell death and parkinsonian motor signs that could be induced by the dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
KeywordsSucrose Dopamine Schizophrenia Hydrochloride Neurol
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