Don't get too excited: mechanisms of glutamate-mediated Purkinje cell death.

摘要: Abstract Purkinje cells (PCs) present a unique cellular profile in both the cerebellum and brain. Because they represent only output cell of cerebellar cortex, play vital role normal function cerebellum. Interestingly, PCs are highly susceptible to variety pathological conditions that may involve glutamate-mediated ‘excitotoxicity', term coined describe an excessive release glutamate, subsequent over-activation excitatory amino acid (NMDA, AMPA, kainite) receptors. Mature PCs, however, lack functional NMDA receptors, means by which Ca 2+ enters classic hippocampal cortical models excitotoxicity. In glutamate predominantly mediates its effects, first via rapid influx through voltage-gated calcium channels, caused depolarization membrane after AMPA receptor activation (and -permeable receptors themselves), second, delayed from intracellular stores. Although physiological levels free initate second messenger signaling pathways can detrimentally alter dendritic spine morphology interactions with neuronal cytoskeleton, thus perturb synaptic function. possess various calcium-bining proteins, such as calbindin-D28K parvalbumin, transporters, order prevent exerting deleterious effects. Bergmann glia gaining recognition key players clearence extracellular glutamate; these also high S-100β, protein neurodegenerative neuroprotective abilities. this review, we discuss PC-specific mechanisms excitotoxic death, relationship between implications S-100β for pathlogical conditions, traumatic brain injury.