Article

Genetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches.

Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 05/1997; 94(8):4103-8. DOI: 10.1073/pnas.94.8.4103
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
73 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In order to understand the pathophysiology of temporal lobe epilepsy (TLE), and thus to develop new pharmacological treatments, in vivo animal models that present features similar to those seen in TLE patients have been developed during the last four decades. Some of these models are based on the systemic administration of chemoconvulsants to induce an initial precipitating injury (status epilepticus) that is followed by the appearance of recurrent seizures originating from limbic structures. In this paper we will review two chemically-induced TLE models, namely the kainic acid and pilocarpine models, which have been widely employed in basic epilepsy research. Specifically, we will take into consideration their behavioral, electroencephalographic and neuropathologic features. We will also evaluate the response of these models to anti-epileptic drugs and the impact they might have in developing new treatments for TLE. Copyright © 2015. Published by Elsevier B.V.
    Journal of Neuroscience Methods 03/2015; DOI:10.1016/j.jneumeth.2015.03.009 · 1.96 Impact Factor
  • Source
    Dataset: 4867.full
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rodent strains used in epilepsy research have various neurological characteristics. These differences were suggested to be attributed to the diverse densities of the ionotropic glutamate receptor (iGluR) subunits. However, previous studies failed to find interstrain differences in the hippocampal receptor levels. We supposed that a detailed layer-to-layer analysis of the iGluR subunits in the hippocampus might reveal strain-dependent differences in their base lines and reactions induced by pilocarpine (PILO) between two mouse strains without documented ancestors. Levels of iGluR subunits in Balb/c and NMRI mice were compared using semiquantitative immunohistochemistry. The alterations in the neuronal circuitry were validated by neuropeptide Y (NPY) and neuronal nuclear antigen (NeuN) immunostainings. Immunohistochemistry showed interstrain laminar differences in some subunits of both the control and PILO-treated animals. The seizure-induced irreversible neuronal changes were accompanied by reduced GluA1 and GluA2 levels. Their changes were inversely correlated in the individual NMRI mice by Pearson's method. Increase in NPY immunoreactivity showed positive correlation with GluA1, and negative correlation with GluA2. The NMRI strain was susceptible to PILO-induced hippocampal sclerosis, while the Balb/c animals showed resistance. Basal levels of iGluRs differ in mouse strains, which may account for the interstrain differences in their reactions to the convulsant. Copyright © 2015. Published by Elsevier B.V.
    Journal of Chemical Neuroanatomy 02/2015; 64. DOI:10.1016/j.jchemneu.2015.02.002 · 2.52 Impact Factor

Full-text (2 Sources)

Download
51 Downloads
Available from
May 17, 2014