Mouse strain differences in kainic acid sensitivity, seizure behavior, mortality, and hippocampal pathology

McKhann, Guy M.; Wenzel, H. Jürgen; Robbins, Carol A.; Sosunov, Alexander A.; Schwartzkroin, Philip A.

doi:10.1016/s0306-4522(03)00562-1

Cited by 180 publications

(184 citation statements)

References 38 publications

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“…Specifically, all mice used in this study were progeny derived from heterozygous by heterozygous matings and therefore all contained the same strain and genetic background. This is an important point to recognize since genetic background and mouse strain has been demonstrated to alter the susceptibility to KA-induced excitotoxicity [38,39,54,55]. For celecoxib pretreatment, PTGS-2 +/+ mice were given free access for six weeks to a diet containing 0, 3000 or 6000 ppm celecoxib.…”

Section: Animal Housingmentioning

confidence: 99%

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Toscano

Ueda

Tomita

et al. 2008

Brain Research Bulletin

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Excitotoxicity involves over activation of brain excitatory glutamate receptors and has been implicated in neurological, neurodegenerative and neuropsychiatric diseases. Metabolism of arachidonic acid (AA) through the phospholipase A 2 (PLA 2 )/ prostaglandin-endoperoxide synthase (PTGS) pathway is increased after excitotoxic stimulation. However, the individual roles of the PTGS isoforms in this process are not well established. We assessed the role of the PTGS isoforms in the process of excitotoxicity by exposing mice deficient in either PTGS-1 (PTGS-1 -/-) or PTGS-2 (PTGS-2 -/-) to the rototypic excitotoxin, kainic acid (KA). Seizure intensity and neuronal damage were significantly elevated in KA-exposed PTGS-2 -/-, but not in PTGS-1 -/-, mice. The increased susceptibility was not associated with an alteration in KA receptor binding activity or mediated through the CB1 endocannabinoid receptor. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was decreased in the CA1 pyramidal neurons of PTGS-2 -/-mice, suggesting an alteration of GABAergic function. In wild-type mice, six weeks treatment with the PTGS-2 selective inhibitor celecoxib recapitulated the increased susceptibility to KA-induced excitotoxicity observed in PTGS-2 -/-mice, further supporting the role of PTGS-2 in the excitotoxic process. The increased susceptibility to KA was also associated with decreased brain levels of PGE 2 , a biomarker of PTGS-2 activity. Our results suggest that PTGS-2 activity and its specific products may modulate neuronal excitability by affecting GABAergic neurotransmission. Further, inhibition of PTGS-2 but not PTGS-1, may increase the susceptibility to seizures.

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Section: Animal Housingmentioning

confidence: 99%

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Toscano

Ueda

Tomita

et al. 2008

Brain Research Bulletin

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“…They suggested that modifier loci could influence the expression of the Foxg1-cre allele or modulate the activity of the Cre recombinase itself (Hebert and McConnell, 2000). Genetic background has long been known to influence the behavioral phenotype of mutant mice (Shanks and Anisman, 1988,Gerlai, 1996,Logue et al, 1997,Bouwknecht and Paylor, 2002,Schauwecker, 2002,McKhann et al, 2003,Sik et al, 2003,Waddell et al, 2004, but fewer studies have focused on the brain-based mechanisms for such strain dependence. Brain (Bilovocky et al, 2003) and limb (Murcia et al, 2004) phenotypes caused by mutation of the Engrailed-1 (en-1) gene are highly dependent upon genetic background, as are the neural phenotypes produced by mutations of p75NGF (Greferath et al, 2000), Unc5c (Burgess et al, 2006), fmr-1 (Paradee et al, 1999,Dobkin et al, 2000,Ivanco and Greenough, 2002,Mineur et al, 2002,Errijgers and Kooy, 2004 and Pax2 (Schwarz et al, 1997).…”

Section: The Influence Of Genetic Background On the Expression Of Phementioning

confidence: 99%

Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon

et al. 2007

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The Cre/loxP system is used routinely to manipulate gene expression in the mouse nervous system. In order to delete genes specifically from the telencephalon, the Foxg1-cre line was created previously by replacing the intron-less Foxg1 coding region with cre, resulting in a Foxg1 heterozygous mouse. As the telencephalon of heterozygous Foxg1 mice was reported to be normal, this genotype often has been used as the control in subsequent analyses. Here we describe substantial disruption of forebrain development of heterozygous mice in the Foxg1-cre line, maintained on the C57BL/6J background. High resolution magnetic resonance microscopy reveals a significant reduction in the volume of the neocortex, hippocampus and striatum. The alteration in the neocortex results, in part, from a decrease in its tangential dimension, although gross patterning of the cortical sheet appears normal. This decrease is observed in three different Foxg1 heterozygous mouse lines, independent of the method of achieving deletion of the Foxg1 gene. Although Foxg1 is not expressed in the diencephalon, three-dimensional magnetic resonance microscopy revealed that thalamic volume in the adult is reduced. In contrast, at postnatal day 4, thalamic volume is normal, suggesting that interactions between cortex and dorsal thalamus postnatally produce the final adult thalamic phenotype. In the Foxg1-cre line maintained on the C57BL/6J background, the radial domain of the cerebral cortex also is disrupted substantially, particularly in supragranular layers. However, neither Foxg1 heterozygous mice of the Foxg1-tet line, nor those of the Foxg1-lacZ and Foxg1-cre lines maintained on a mixed background, displayed a reduced cortical thickness. Thus Cre recombinase contributes to the radial phenotype, although only in the context of the congenic C57BL/6J background. These observations highlight an important role for Foxg1 in cortical development, reveal noteworthy complexity in the invocation of specific mechanisms underlying phenotypes expressed following genetic manipulations and stress the importance of including appropriate controls of all genotypes. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Development of the cerebral cortex relies on extracellular cues and intrinsic signals that instruct the proliferation, differentiation and migration of neuronal precursors. The duration and location of these cues are critical to producing the final cortical architecture (FukuchiShimogori and Grove, 2001, Parnavelas et al., 2002, Rakic, 2002, Shimogori et al., 2004, Rash and Grove, 2006, Storm et al., 2006. The...

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“…In keeping with this, the chance that persistent alterations of brain excitability, lasting during ecstasy withdrawal, might predispose to subsequent seizures has never been considered. In particular, clinical and basic research never questioned whether MDMA abuse might produce delayed altered brain excitability including convulsive seizures.In the present study, by profiting from an experimental model with low sensitivity to limbic seizures (C57Black mice, McKhann et al, 2003), we investigated whether pure MDMA induces per se long-term changes in brain excitability as documented by alterations of EEG, epileptic threshold and latent metabolic hyperexcitability.In detail we addressed the following points: 1) whether MDMA intake produces persistent EEG alterations; 2) whether epileptic seizures are facilitated and they occur …”

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confidence: 99%

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

et al. 2005

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Mouse strain differences in kainic acid sensitivity, seizure behavior, mortality, and hippocampal pathology

Cited by 180 publications

References 38 publications

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

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