Initiation, Propagation and Generalization of Paroxysmal Discharges in an Epileptic Mutant Animal

Suzuki, Jirô; Kasamo, Kimihiro; Ishida, Nobuya; Murashima, Yoshiya L.

doi:10.1111/j.1440-1819.1991.tb02470.x

Cited by 8 publications

(7 citation statements)

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“…The importance of synaptic zinc in contributing to seizure activity has been clearly supported by animal models of epilepsy (Foresti et al, 2008;Flynn et al, 2007;Frederickson et al, 1988;Frederickson, 1989;Sloviter, 1985;Suh et al, 2001;Takeda et al, 2003) including the epilepsy-like (EL) mouse. Seizures in EL mice commence with the onset of puberty, originate in or near the parietal lobe, and then spread to the hippocampus and to other brain regions (Ishida et al, 1993;Suzuki et al, 1991;Todorova et al, 1999;Uchibori et al, 2002). The observation that zinc concentration is significantly lower in the hippocampal dentate area of EL mice as compared to that of control mice (Fukahori et al, 1988) suggests that a decrease of hippocampal zinc may be involved in the pathophysiology of convulsive seizures in the EL mice.…”

Section: Epilepsymentioning

confidence: 98%

Zinc: The brain's dark horse

Bitanihirwe

Cunningham

2009

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Zinc is a life-sustaining trace element, serving structural, catalytic, and regulatory roles in cellular biology. It is required for normal mammalian brain development and physiology, such that deficiency or excess of zinc has been shown to contribute to alterations in behavior, abnormal central nervous system development, and neurological disease. In this light, it is not surprising that zinc ions have now been shown to play a role in the neuromodulation of synaptic transmission as well as in cortical plasticity. Zinc is stored in specific synaptic vesicles by a class of glutamatergic or "gluzinergic" neurons and is released in an activity-dependent manner. Because gluzinergic neurons are found almost exclusively in the cerebral cortex and limbic structures, zinc may be critical for normal cognitive and emotional functioning. Conversely, direct evidence shows that zinc might be a relatively potent neurotoxin. Neuronal injury secondary to in vivo zinc mobilization and release occurs in several neurological disorders such as Alzheimer's disease and amyotrophic lateral sclerosis, in addition to epilepsy and ischemia. Thus, zinc homeostasis is integral to normal central nervous system functioning, and in fact its role may be underappreciated. This article provides an overview of zinc neurobiology and reviews the experimental evidence that implicates zinc signals in the pathophysiology of neuropsychiatric diseases. A greater understanding of zinc's role in the central nervous system may therefore allow for the development of therapeutic approaches where aberrant metal homeostasis is implicated in disease pathogenesis.

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Section: Epilepsymentioning

confidence: 98%

Zinc: The brain's dark horse

Bitanihirwe

Cunningham

2009

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236

154

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“…EL mice experience complex partial seizures with secondary generalization similar to those seen in humans [6,10]. Seizures in EL mice commence with the onset of puberty (50–60 days), originate in or near the parietal lobe, and then spread to the hippocampus and to other brain regions [6,11-13]. The seizures are accompanied by electroencephalographic abnormalities, vocalization, incontinence, loss of postural equilibrium, excessive salivation, and head, limb, and chewing automatisms [10,12,14-17].…”

Section: Introductionmentioning

confidence: 99%

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et al. 2004

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BackgroundThe high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period.ResultsBody weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups.ConclusionsThe results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.

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“…EL mice experience complex partial seizures with secondary generalizations (Seyfried & Glaser, 1985; Brigande et al., 1989). The seizures in EL mice originate either in or near the parietal lobe (Suzuki et al., 1991; Kasamo et al., 1992; Ishida et al., 1993) or hippocampus (Mutoh et al., 1993) and generalize to other brain regions. The seizures are accompanied by abnormalities such as vocalizations; incontinence; loss of postural equilibrium (Straub tail); excessive salivation; and head, limb, swallowing, and chewing automatisms (Suzuki, 1976; Suzuki & Nakamoto, 1977; Sato, 1985; Ishida et al., 1993; Nakano et al., 1994; Seyfried et al., 1999; Todorova et al., 1999).…”

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confidence: 99%

The EL mouse: A natural model of autism and epilepsy

2011

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SUMMARYPurpose: Autism is a multifactorial disorder that involves impairments in social interactions and communication, as well as restricted and repetitive behaviors. About 30% of individuals with autism develop epilepsy by adulthood. The EL mouse has long been studied as a natural model of multifactorial idiopathic generalized epilepsy with complex partial seizures. Because epilepsy is a comorbid trait of autism, we evaluated the EL mouse for behaviors associated with autism. Methods: We compared the behavior of EL mice to agematched control DDY mice, a genetically related nonepileptic strain. The mice were compared in the open field and in the light-dark compartment tests to measure activity, exploratory behavior, and restricted and repetitive behaviors. The social transmission of food preference test was employed to evaluate social communication. Home-cage behavior was also evaluated in EL and DDY mice as a measure of repetitive activity.Key Findings: We found that EL mice displayed several behavioral abnormalities characteristic of autism. Impairments in social interaction and restricted patterns of interest were evident in EL mice. Activity, exploratory behavior, and restricted behavior were significantly greater in EL mice than in DDY mice. EL mice exhibited impairment in the social transmission of food preference assay. In addition, a stereotypic myoclonic jumping behavior was observed in EL mice, but was not seen in DDY mice. It is of interest to note that seizure activity within 24 h of testing exacerbated the autistic behavioral abnormalities found in EL mice. Significance: These findings suggest that the EL mouse expresses behavioral abnormalities similar to those seen in persons with autism. We propose that the EL mouse can be utilized as a natural model of autism and epilepsy.

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Initiation, Propagation and Generalization of Paroxysmal Discharges in an Epileptic Mutant Animal

Cited by 8 publications

References 1 publication

Zinc: The brain's dark horse

Zinc: The brain's dark horse

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The EL mouse: A natural model of autism and epilepsy

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