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Symptoms of Parkinson's disease (akinesia, muscle rigidity and tremor) result from degeneration of dopaminergic nigrostriatal pathway. Furthermore, a shift of dopaminergic-glutamatergic balance towards overactivation of glutamatergic systems exists in this disease. Therefore, drugs which inhibit glutamatergic transmission were expected to have antiparkinsonian impact. Our studies showed that the blockade of the group I mGluRs (mGluR1 and 5) in the striatum decreased catalepsy and muscle rigidity in the haloperidol-induced animal models of parkinsonism, which seemed to be due to inhibition of the indirect striopallidal pathway. On the contrary, systemic injections of mGluR5 antagonists did not infl uence the tacrine-induced tremor and diminished functioning of the nigrostriatal pathway. Moreover, the mGluR1 antagonist strongly enhanced the tremor induced by harmaline. Agonists of groups II and III mGluRs exerted antiparkinsonianlike effects which differed depending on their brain targets. Agonists of the group II seemed to act at the level of the subthalamo-nigral glutamatergic synapses, but not in the striatum, whereas an antiakinetic effect of agonists of group III was strong in the globus pallidus and striatum, but weak or none in the substantia nigra. The above results seem to suggest that because of a wide distribution of mGluRs in the brain, ligands of these receptors may exhibit limited effi ciency as antiparkinsonian drugs in humans.
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Czy chorobę Alzheimera można wyleczyć?

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Stanisław Wolfarth graduated at the Medical Academy in Kraków in 1963. He worked for over 40 years at the Institute of Pharmacology PAS, where he was a head of the Department of Neuropharmacology (1971–2003). Studies on the role of the basal ganglia in development of Parkinson’s disease became a passion of his life. One of his fi rst achievements was the fi nding that clinical relationship termed dopaminergic-cholinergic balance resulted from interactions of complex neuronal systems including the substantia nigra, striatum and other structures. He demonstrated that GABAergic pathways connecting the substantia nigra, thalamus and zona incerta - lateral hypothalamus controlled the muscle tone, and played a crucial role in initiation of movements. He was one of the authors of a prototypic device for objective measurement of the muscle tone of rat’s hind paw which is now the only apparatus of this type worldwide. Within the last 15 years he found antiparkinsonian properties of ligands of NMDA and metabotropic glutamate receptors in animal models, and discovered that muscle stiffness in the elderly had completely different pathophysiological basis than parkinsonian muscle rigidity. He was deeply involved in several international co-operations, was an author of over 90 scientifi c papers, and for his pioneer discoveries was highly prized by many scientifi c organizations. His works are characterized by amazing coherence of research objectives, consistency and up-to-dateness.
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