Calpain-mediated P35 to P25 conversion is induced by neurotoxic processes and amyloid βtreatment

Abstract

Entry of calcium through N-methyl-d-aspartate-type glutamate receptors in the caudate–putamen nucleus is essential for normal motor activity, but can produce cytotoxicity with continued stimulation and subsequent release of intracellular calcium. To determine potential functional sites for N-methyl-d-aspartate receptor activation in this region, we examined the ultrastructural localization of the R1 subunit of the N-methyl-d-aspartate receptor (NMDAR1) in rat brain. In addition, we comparatively examined the localization of NMDAR1 and sorcin, a 22,000 mol. wt calcium binding protein present in certain striatal neurons and involved in calcium-induced calcium release. NMDAR1-like immunoreactivity was seen at synaptic and non-synaptic sites on neuronal plasma membranes. Of 1 514 NMDAR1-labeled profiles, 62% were dendrites and dendritic spines and the remainder were mainly unmyelinated axons and axon terminals. Sorcin-like immunoreactivity was present in 39% of the profiles that contained NMDAR1 labeling, most (533/595) of which were dendrites and dendritic spines. Of 1 807 sorcin-labeled profiles, 42% were identified, however, as small processes including spine necks and unmyelinated axons or axon terminals. These profiles also occasionally contained NMDAR1 or showed synaptic or appositional contacts with other NMDAR1-immunoreactive neurons.The results of this study suggest that in the caudate–putamen nucleus, activation of NMDA receptors permits calcium influx at plasmalemmal sites mainly on dendrites where sorcin may play a role in calcium-induced calcium release. The presence of sorcin in some, but not all NMDA-containing neurons in the caudate–putamen nucleus has potential implications for the known differential vulnerability of certain striatal neurons to excitotoxins.