Faculty Collaboration Database

Selective vulnerability of hippocampal sub-fields to oxygen-glucose deprivation is a function of animal age. Brain Res 2014 Jan 16;1543:271-9

Date

11/12/2013

Pubmed ID

24211659

DOI

10.1016/j.brainres.2013.10.056

Scopus ID

2-s2.0-84891745130 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

For more than a century, the hippocampal sub-fields have been recognized as being differentially vulnerable to injury. While the cause remains unknown, the explanations generally considered have involved either vascular differences, or innate variability among cells. To examine the latter possibility, we prepared acute hippocampal slices from Sprague-Dawley rats, applied a brief period of oxygen-glucose deprivation (OGD; an in vitro model of ischemia), and assessed the viability of dissected sub-fields (CA1, CA3, dentate gyrus) by measuring mitochondrial 2,3,5-triphenyltetrazolium chloride (TTC) metabolism. In slices from young animals (15 weeks of age), post-OGD TTC metabolism was significantly reduced in the CA sub-fields relative to the dentate gyrus. Since previous studies found increasing age may worsen ischemic injury, we completed the same experiment using tissue from animals at 52 weeks of age, and found no differences in TTC metabolism across sub-fields. Given the established role of glutamate receptors in ischemic cell death, we examined two key subunit proteins (GluN1, found in all NMDA receptors, and GluA2, found in most AMPA receptors) across sub-fields and age to determine whether their expression complemented our viability data. We found that, relative to the CA1, the DG displayed greater GluN1 expression and lower GluA2 expression in both young and old animals. Our results confirm that regional vulnerability can be shown in a slice model, that the property is not intransigent, and that these features are likely not attributable to the expression pattern of key glutamate receptor subunits, but another molecular variable that changes over the lifespan.

Author List

Lalonde CC, Mielke JG

Author

Crystal C. Lalonde MD Assistant Professor in the Family Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Analysis of Variance
Animals
Glucose
Hippocampus
Hypoxia
In Vitro Techniques
L-Lactate Dehydrogenase
Male
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Receptors, N-Methyl-D-Aspartate
Tetrazolium Salts