tailieunhanh - Parkinson disease and related disorders part - part 10

Dự vỏ não trung gai striatopallidal (GABAergic) và interneurons aspiny lớn striatal (cholinergic) sử dụng glutamate như chất dẫn truyền thần kinh quan trọng của họ. Đường nigrostriatal dopaminergic phát sinh từ SNpc phục vụ để điều chỉnh các hiệu ứng kích thích đầu vào vỏ não trên tế bào thần kinh striatal. | 558 C. HENCHCLIFFE AND M. F. BEAL In this condition voltage-dependent magnesium blockade is lost and calcium influx may occur through the NMDA receptor-linked channel despite near-physiologic levels of glutamate. If sufficient the elevated intracellular calcium concentration would induce free radical formation by mitochondria activate NOS and thereby cause oxidative damage to proteins lipids and DNA. Mitochondrial damage sustained would then further compromise energy metabolism and could potentially lead to a cycle of increasing excitotoxic damage and metabolic compromise. In cultured rat cerebellar neurons energy depletion caused by absence of oxygen glucose inhibitors of oxidative phosphorylation or sodium potassium ATPase activity results in a lowered threshold for excitotoxic damage due to elevated glutamate levels Novelli et al. 1988 . This is consistent with the model of slow excitotoxicity discussed above. Inhibition of glycolysis by iodoacetate or of oxidative phosphorylation by cyanide a complex IV inhibitor in cultured chick retina likewise results in excitotoxicity without increased extracellular glutamate concentration via NMDA receptor activation Zeevalk and Nicklas 1991 . Cultured hippocampal or cortical neurons are more susceptible to excitotoxicity following cyanide treatment Dubinsky and Rothman 1991 . Moreover hyperpolarizing the cell membrane by using potassium channel activators is protective against excitotoxicity in cultured cells Abele and Miller 1990 . . Glutamate in motor pathways and in Parkinson s disease The striatum plays a pivotal role in motor control and influences efferent output from the globus pallidus interna GPi and SNpr via the direct and indirect pathways. The direct pathway consists of a GABAergic projection from striatum to GPi and SNpr. The indirect pathway comprises striatal output via GABAergic projections to the globus pallidus externa GPe that in turn sends GABAergic projections to the STN. The STN in turn has .

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