Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor

Turner, Laura H.; Lim, Chen E.; Heinrichs, Stephen C.

doi:10.1016/j.yebeh.2006.08.013

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…These findings are consistent with previous work characterizing EL mice as having low or abnormal sociability in various other paradigms [50,61–63]. Notably, after KD feeding, females became highly social in the 3-chamber test; there was moderately increased sociability in males.…”

Section: Discussionsupporting

confidence: 92%

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

Ruskin

Fortin

Bisnauth

et al. 2017

Physiology & Behavior

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The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients. This study tests the behavioral effects of ketogenic diet feeding in the EL mouse, a model with behavioral characteristics of autism spectrum disorder and comorbid epilepsy. Male and female EL mice were fed control diet or one of two ketogenic diet formulas ad libitum starting at 5 weeks of age. Beginning at 8 weeks of age, diet protocols continued and performance of each group on tests of sociability and repetitive behavior was assessed. A ketogenic diet improved behavioral characteristics of autism spectrum disorder in a sex- and test-specific manner; ketogenic diet never worsened relevant behaviors. Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice, with limited effects in males. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females.

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Section: Discussionsupporting

confidence: 92%

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

Ruskin

Fortin

Bisnauth

et al. 2017

Physiology & Behavior

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“…Our results of stereotypic behaviors and impaired communication, together with previous reports of social deficits in EL mice (Lim et al., 2007; Turner et al., 2007), are the first to demonstrate salient abnormalities relevant to all three diagnostic components of autism in EL mice. This, along with other abnormalities relevant to autism (Table 2), highlights the value of the EL mouse as a model of autism and epilepsy.…”

Section: Discussionsupporting

confidence: 79%

“…EL mice exhibit short‐term memory deficits in social investigation with juvenile conspecific mice (Lim et al., 2007). EL mice also exhibit a deficit in interacting with and investigating an unfamiliar adult mouse in a novel cage environment (Turner et al., 2007). These findings indicate that EL mice exhibit impaired social interactions.…”

mentioning

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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“…Remarkably, the breeding processes used to create heightened seizure sensitivity in both colonies simultaneously produced robust, comorbid ASD-like traits. Both FAST rats and EL mice exhibit significant social impairment (Reinhart et al, 2004, 2006; Gilby et al, 2007; Lim et al, 2007; Turner et al, 2007) and repetitive behaviors (e.g., overgrooming, self-injurious scratching, and/or myoclonic jumping; Gilby, 2008; Meidenbauer et al, 2011) alongside delays in social, physical, and visuomotor development (McFadyen-Leussis and Heinrichs, 2005), learning deficits, impulsivity, and hyperactivity in various testing paradigms (Anisman and McIntyre, 2002; McFadyen-Leussis and Heinrichs, 2005; Azarbar et al, 2010). FAST rats are also more aggressive than their comparison (SLOW) strain (Reinhart et al, 2004, 2006) and show reduced acoustic startle but enhanced fear conditioning (Anisman et al, 2000).…”

Section: Animal Models Of Asdmentioning

confidence: 99%

Studying Autism in Rodent Models: Reconciling Endophenotypes with Comorbidities

Argyropoulos¹,

Gilby²,

Hill‐Yardin³

2013

Front. Hum. Neurosci.

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Autism spectrum disorder (ASD) patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing, and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the core diagnostic traits (social communication deficits and repetitive behaviors). Studying endophenotypes relevant to both core and comorbid features of ASD in rodent models can provide insight into biological mechanisms underlying these disorders. Here we review the characterization of endophenotypes in a selection of environmental, genetic, and behavioral rodent models of ASD. In addition to exhibiting core ASD-like behaviors, each of these animal models display one or more endophenotypes relevant to comorbid features including altered sensory processing, seizure susceptibility, anxiety-like behavior, and disturbed motor functions, suggesting that these traits are indicators of altered biological pathways in ASD. However, the study of behaviors paralleling comorbid traits in animal models of ASD is an emerging field and further research is needed to assess altered gastrointestinal function, aggression, and disorders of sleep onset across models. Future studies should include investigation of these endophenotypes in order to advance our understanding of the etiology of this complex disorder.

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Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor

Cited by 18 publications

References 33 publications

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

The EL mouse: A natural model of autism and epilepsy

Studying Autism in Rodent Models: Reconciling Endophenotypes with Comorbidities

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