Genes on distal chromosome 18 determine vulnerability to excitotoxic neurodegeneration following status epilepticus, but not striatal neurodegeneration induced by quinolinic acid.
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.
McLin
Jessica Pilar
JP
Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA 92697, USA. jessica.mclin@yahoo.com
Thompson
Leslie Michels
LM
Lusis
Aldons J
AJ
Davis
Richard C
RC
Steward
Oswald
O
D000818:Animals; D033481:Chromosomes, Mammalian / Q000187:drug effects / Q000235:genetics*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004198:Disease Susceptibility / Q000139:chemically induced / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D017378:Quinolinic Acid / Q000633:toxicity*; D013045:Species Specificity; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D018690:Excitatory Amino Acid Agonists; D017378:Quinolinic Acid