Genes on distal chromosome 18 determine vulnerability to excitotoxic neurodegeneration following status epilepticus, but not striatal neurodegeneration induced by quinolinic acid

Jessica Pilar McLin; Leslie Michels Thompson; Aldons J. Lusis; Richard C. Davis; Oswald Steward

Neurobiology of Disease (Mar 2008)

Genes on distal chromosome 18 determine vulnerability to excitotoxic neurodegeneration following status epilepticus, but not striatal neurodegeneration induced by quinolinic acid

Jessica Pilar McLin,
Leslie Michels Thompson,
Aldons J. Lusis,
Richard C. Davis,
Oswald Steward

Affiliations

Jessica Pilar McLin: Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA; Corresponding author. 256 Halfmoon Court, West New York, NJ 07093, USA.
Leslie Michels Thompson: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA; Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
Aldons J. Lusis: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles School of Medicine, Los Angeles, CA 90095-1679, USA
Richard C. Davis: Department of Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095-1679, USA
Oswald Steward: Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA 92697, USA; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA; Department of Neurosurgery, University of California, Irvine, Irvine, CA 92697, USA

Journal volume & issue: Vol. 29, no. 3
pp. 391 – 399

Abstract

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Previous studies have provided evidence that a quantitative trait locus (QTL) on the distal part of chromosome 18 (chr18) is a major determinant of vulnerability to hippocampal neurodegeneration following kainic acid (KA)-induced seizures in inbred mouse strains. We assessed excitotoxic vulnerability in two congenic, “genome tagged” mouse strains carrying segments of either distal or proximal/medial chr18 from vulnerable DBA/2J mice on a resistant C57BL/6 background. Systemic KA injections triggered brain-wide neurodegeneration in the distal chr18 congenic strain, and specifically in the hilus of the dentate gyrus, but not in CA3. In contrast, the proximal/medial chr18 congenic strain exhibited enhanced degeneration in CA1 and CA3, but little neurodegeneration elsewhere. Both strains exhibited low levels of QUIN-induced striatal neurodegeneration comparable to what is seen in C57BL/6 mice. These results suggest that gene(s) on distal chr18 are important determinants of vulnerability to KA-induced hippocampal neurodegeneration, but not QUIN-induced striatal neurodegeneration.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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