Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures

Abstract

Brain ischemia leads to overstimulation of N-methyl-D-aspartate (NMDA) receptors, referred as excitotoxicity, which mediates neuronal cell death. However, less attention has been paid to changes in synaptic activity and morphology that could have an important impact on cell function and survival following ischemic insult. In this study, we investigated the effects of reperfusion after oxygen/glucose deprivation (OGD) not only upon neuronal cell death, but also on ultrastructural and biochemical characteristics of postsynaptic density (PSD) protein, in the stratum lucidum of the CA3 area in organotypic hippocampal slice cultures. After OGD/reperfusion, neurons were found to be damaged; the organelles such as mitochondria, endoplasmic reticulum, dendrites, and synaptic terminals were swollen; and the PSD became thicker and irregular. Ethanolic phosphotungstic acid staining showed that the density of PSD was significantly decreased, and the thickness and length of the PSD were significantly increased in the OGD/reperfusion group compared to the control. The levels of PSD proteins, including PSD-95, NMDA receptor 1, NMDA receptor 2B, and calcium/calmodulin-dependent protein kinase II, were significantly decreased following OGD/reperfusion. These results suggest that OGD/reperfusion induces significant modifications to PSDs in the CA3 area of organotypic hippocampal slice cultures, both morphologically and biochemically, and this may contribute to neuronal cell death and synaptic dysfunction after OGD/reperfusion.

Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment

“…NMDA glutamate receptors participate in learning and memory. Overstimulation of these receptors by excess of glutamate can cause cell death during glucose and oxygen deprivation (Jung et al, 2012 ) and memory deficits due to xenobiotic exposure (Olney et al, 2000 ; Li et al, 2012 ). L-cys 2/ L-glu, L-cys and L-glu transporters participate in GSH synthesis in the CNS and are modulated by oxidative stress.…”

Regional and time-dependent neuroprotective effect of hypothermia following oxygen-glucose deprivation

“…This vulnerability has been associated with postischemic expression of GluR2 lacking Ca ++ permeable receptors at CA1 synapses (Colbourne et al, ) and to hyperexcitability of the CA3 afferents (Ye et al, ). Yet morphological and biochemical modifications have been demonstrated in the CA3 area after OGD (Dennis et al, ; Jung et al, ) while delayed neuronal death has been demonstrated on in vitro DG granular cells after long glucose deprivation (Newell et al, ) or after OGD preceded by high glucose preincubation (Rytter et al, ).…”

Airway Smooth Muscle Sensitivity to Methacholine in Precision-Cut Lung Slices (PCLS) from Ovalbumin-induced Asthmatic Mice

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