Cerebral ischemia causes dysregulation of synaptic adhesion in mouse synaptosomes.

Full Abstract

Synaptic pathology is observed during hypoxic events in the central nervous system in the form of altered dendrite structure and conductance changes. These alterations are rapidly reversible, on the return of normoxia, but are thought to initiate subsequent neuronal cell death. To characterize the effects of hypoxia on regulators of synaptic stability, we examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice. We focused on events preceding the onset of ischemic neuronal cell death (<48 h). Synaptosome preparations were enriched in synaptically localized proteins and were free of endoplasmic reticulum and nuclear contamination. Electron microscopy showed that the synaptosome preparation was enriched in spheres (approximately 650 nm in diameter) containing secretory vesicles and postsynaptic densities. Forebrain mRNA levels of synaptically located CAMs was unaffected at 3 h after MCAO. This is contrasted by the observation of consistent downregulation of synaptic CAMs at 20 h after MCAO. Examination of synaptosomal CAM protein content indicated that certain adhesion molecules were decreased as early as 3 h after MCAO. For comparison, synaptosomal Agrn protein levels were unaffected by cerebral ischemia. Furthermore, a marked increase in the levels of p-Ctnnb1 in ischemic synaptosomes was observed. p-Ctnnb1 was detected in hippocampal fiber tracts and in cornu ammonis 1 neuronal nuclei. These results indicate that ischemia induces a dysregulation of a subset of synaptic proteins that are important regulators of synaptic plasticity before the onset of ischemic neuronal cell death.

Author information

Author/s: Costain, Willard J (WJ); Rasquinha, Ingrid (I); Sandhu, Jagdeep K (JK); Rippstein, Peter (P); Zurakowski, Bogdan (B); Slinn, Jacqueline (J); MacManus, John P (JP); Stanimirovic, Danica B (DB);

Affiliation: Glycosyltransferase and Neuroglycomics, Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada. Will.Costain(-atsign-)nrccnrc.gc.ca

Journal and publication information

Publication Type: Journal Article

Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab), published in United States. (Language: eng)

Reference: 2008-Jan; vol 28 (issue 1) : pp 99-110

Dates: Created 2007/12/21; Completed 2008/03/10;

PMID: 17519975, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: 18 Feb 2009 00:00:00)

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