课件：帕金森病和运动障碍疾病.ppt

Slide 3. Aetiology of Parkinsons disease ? ·??????? The different genetic and environmental factors involved in Parkinsons disease collectively cause progressive degeneration of the substantia nigra pars compacta. ? ·??????? The substantia nigra pars compacta is responsible for the tonic dopaminergic stimulation of various sites in the basal ganglia and cortex at a steady rate of about 4-5 pulses per second. Loss of this stimulatory function is the primary cause of the classical symptoms of Parkinsons disease ? ·??????? Lewy bodies are also associated with most cases of Parkinsons disease but their relationship to pathogenesis is not clear Neuroanatomy of the Basal Ganglia The basal ganglia are a group of nuclei lying deep in the subcortical white matter of the frontal lobes that organize motor behavior. Due to their subcortical location, the basal ganglia are ideally situated to provide communication between the cortex and thalamus via a feedback loop. Sensorimotor information from the cortex is processed by the basal ganglia, which consists of the striatum, the internal globus pallidus (GPi), the external globus pallidus (GPe), the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr). Cortical information is relayed to the striatum (the “input” nuclei) via glutamatergic neurons. This cortical information is regulated within tight controls by a constant dopaminergic input from the substantia nigra pars compacta (SNc). Therefore, adequate amounts of dopamine are key for the proper functioning of this complex neuronal network. Parent et al. Trends Neurosci 1993: 16; 111–115. Dopaminergic therapy with levodopa or dopamine agonists is the cornerstone of symptomatic management of Parkinson’s disease. As can be seen in the next slide, levodopa replaces dopamine presynaptically, while dopamine agonists act directly on receptors post-synaptically. Levodopa is administered with a peripheral decarboxylase inhibitor, either benserazide or carb