Prior deafferentation confers long term protection to CA1 against transient forebrain ischemia and sustains GluR2 expression.
Hippocampal CA1 pyramidal neurons undergo delayed neurodegeneration after transient forebrain ischemia, and the phenomenon is dependent upon hyperactivation of l-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype of glutamate receptors, resulting in aberrant intracellular calcium influx. The GluR2 subunit of AMPA receptors is critical in limiting the influx of calcium. The CA1 pyramidal neurons are very sensitive to ischemic damage and attempts to achieve neuroprotection, mediated by drugs, have been unsuccessful. Moreover, receptor antagonism strategies in the past have failed to provide long-term protection against ischemic injury. Long-term protection against severe forebrain ischemia can be conferred by fimbria-fornix (FF) deafferentation, which interrupts the afferent input to CA1. Our study evaluated the long-term protective effect of FF deafferentation, 12 days prior to induction of ischemia, on vulnerable CA1 neurons. Our results indicate that at 7 and 28 days post-ischemia, prior FF deafferentation protected 60% of neurons against ischemic cell death. Furthermore, we sought to evaluate whether FF deafferentation also sustained GluR2 levels in these neurons. GluR2 protein and mRNA expression were sustained by deafferentation at 70% of control following ischemia. Correlation studies revealed a positive correlation between GluR2 protein and mRNA level. These results demonstrate that protection conferred by FF deafferentation was long-term and related to sustained GluR2 expression.
Hotchkiss Brain Institute and Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, 157-3330 Hospital Drive NW, Calgary, AB, Canada T2N 2T8.
Jaspreet
J
Kaur
Zonghang
Z
Zhao
Rose M
RM
Geransar
Michalis
M
Papadakis
Alastair M
AM
Buchan
D000344:Afferent Pathways / Q000502:physiology* / Q000503:physiopathology; D000818:Animals; D002339:Carotid Arteries / Q000503:physiopathology; D020712:Fornix, Brain / Q000502:physiology*; D006624:Hippocampus / Q000293:injuries / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D016548:Prosencephalon / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2