Mouse strain differences in kainic acid sensitivity, seizure behavior, mortality, and hippocampal pathology.
Genetic influences contribute to susceptibility to seizures and to excitotoxic injury, but it is unclear if/how these susceptibilities are linked. This study assessed the impact of genetic background on mouse strain seizure susceptibility, seizure phenotype, mortality, and hippocampal histopathology. A subcutaneous (s.c.) kainic acid multiple injection protocol was developed. Five mouse strains were tested: a and b) C57BL/6J and 129/SvJ, strains commonly used in gene targeting experiments; c) C3HeB/FeJ, a strain with reported sensitivity to the convulsant effects of kainic acid (KA); d) 129/SvEms, a strain reportedly susceptible to hippocampal excitotoxic cell death; and e) a mixed genetic background strain (129/SvJXC57BL/6J) from which targeted gene deletion experiments have been carried out. Histopathological features were examined at early (7-10 day), delayed (2-4 month), and late (6-13 month) time points.Mouse background strains can be genetically segregated based on excitotoxin sensitivity, seizure phenotype, mortality, and hippocampal histopathology. When injected with KA, C3HeB/FeJ and C57BL/6J strains were resistant to cell death and synaptic reorganization despite severe behavioral seizures, while 129/SvEms mice developed marked pyramidal cell loss and mossy fiber sprouting despite limited seizure activity. The mixed background 129/SvJXC57BL/6J group exhibited features of both parental strains. In the mouse strains tested, the duration or severity of seizure activity was not predictive of subsequent hippocampal pyramidal cell death and/or synaptic reorganization. Unlike rats, mice exhibiting prolonged high-grade KA-induced seizure activity did not develop subsequent spontaneous behavioral seizures.
McKhann
G M
GM
Department of Neurological Surgery, Columbia University, 710 West 168th Street, NI-42, New York, NY 10032, USA. gm317@colombia.edu
Wenzel
H J
HJ
Robbins
C A
CA
Sosunov
A A
AA
Schwartzkroin
P A
PA
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics* / Q000401:mortality; D013045:Species Specificity
D007608:Kainic Acid