Schauwecker PE, Steward OGenetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches. Proc Natl Acad Sci USA 94:4103-4108

University of Virginia, Charlottesville, Virginia, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/1997; 94(8):4103-8. DOI: 10.1073/pnas.94.8.4103
Source: PubMed


Recent studies have sought to identify the genes involved in excitotoxic neurodegeneration. Here we report that certain strains of mice, including strains that are used for gene targeting studies, do not exhibit excitotoxic cell death after kainic acid seizures. Kainic acid produced excitotoxic cell death in the CA3 and CA1 subfields of the hippocampus in 129/SvEMS and FVB/N mice, in the same pattern as described in rats. C57BL/6 and BALB/c mice exhibited excitotoxic cell death only at very high doses of kainate, and then only in a very restricted area, although they exhibited comparable seizures. Hybrids of 129/SvEMS x C57BL/6 mice created using embryonic stem cells from 129/SvEMS mice also did not exhibit excitotoxic cell death. These results demonstrate that C57BL/6 and BALB/c strains carry gene(s) that convey protection from glutamate-induced excitotoxicity. This differential susceptibility to excitotoxicity represents a potential complication for gene targeting studies.

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    • "Kainic acid-and saline-injected Apoe Ϫ/Ϫ and wild-type mice served as additional controls. Inspection of hematoxylin/eosin-stained sections revealed no obvious neuronal loss in the hippocampus or neocortex of any of the kainic acid-injected groups of mice (data not shown), consistent with a previous study reporting that the C57BL/6J strain is resistant to excitotoxin-induced loss of neuronal cell bodies (Schauwecker and Steward, 1997 "
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    • "Since the Tg tauP301L mice used in our study have an FvB/N background and the PS19 tau Tg mice used in the Iba et al. study are maintained on a B6C3 background, different susceptibility of the hippocampal neurons to tau toxicity might reflect an increased endogenous excitotoxic vulnerability in the FvB/N background. Such increased excitotoxic vulnerability could also explain the observed region specific neuronal vulnerability in our study, since hippocampal neurons are known to be most vulnerable to excitotoxic insults (Schauwecker and Steward, 1997; Mckhann et al., 2003; Liu et al., 2012b). In this regard, previous studies have indicated a role for synaptic dendritic tau in the regulation of neuronal excitability. "
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    • "However, following KA injection, 129SvJ mice had mild SE, and FJ-B labeling showed limited cell loss in the hippocampus following KA, which was probably due to the severity of SE. These data are consistent with the resistance of some mouse strains (e.g., C57Bl/6) to KA-induced cell death in the hippocampus (Schauwecker and Steward, 1997). Because we found that KA injection in mice can elicit only mild SE relative to pilocarpine by EEG, the lack of cell death after KA could be due to the inability to increase the electrical activity sufficiently to initiate excitotoxic mechanisms. "
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