Neuroanatomical differences in FAST and SLOW rat strains with differential vulnerability to kindling and behavioral comorbidities

Pragati Sharma, Stefanie Dedeurwaerdere, Michael A.D. Vandenberg, Ke Fang, Leigh A. Johnston, Sandy R. Shultz, Terence J. O'Brien, Krista L. Gilby

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective The neurobiological factors underlying a predisposition towards developing epilepsy and its common behavioral comorbidities are poorly understood. FAST rats are a strain that has been selectively bred for enhanced vulnerability to kindling, while the SLOW strain has been bred to be resistant to kindling. FAST rats also exhibit behavioral traits reminiscent of those observed in neurodevelopmental disorders (autism spectrum disorder (ASD)/attention-deficit/hyperactivity disorder (ADHD)) commonly comorbid with epilepsy. In this study, we aimed to investigate neuroanatomical differences between these strains that may be associated with a differential vulnerability towards these interrelated disorders. Methods Ex vivo high-resolution magnetic resonance imaging on adult male FAST and SLOW rat brains was performed to identify morphological differences in regions of interest between the two strains. Behavioral examination using open-field, water consumption, and restraint tests was also conducted on a subgroup of these rats to document their differential ASD/ADHD-like behavior phenotype. Using optical stereological methods, the volume of cerebellar granule, white matter, and molecular layer and number of Purkinje cells were compared in a separate cohort of adult FAST and SLOW rats. Results Behavioral testing demonstrated hyperactivity, impulsivity, and polydipsia in FAST versus SLOW rats, consistent with an ASD/ADHD-like phenotype. Magnetic resonance imaging analysis identified brain structural differences in FAST compared with SLOW rats, including increased volume of the cerebrum, corpus callosum, third ventricle, and posterior inferior cerebellum, while decreased volume of the anterior cerebellar vermis. Stereological measurements on histological slices indicated significantly larger white matter layer volume, reduced number of Purkinje cells, and smaller molecular layer volume in the cerebellum in FAST versus SLOW rats. Significance These findings provide evidence of structural differences between the brains of FAST and SLOW rats that may be mechanistically related to their differential vulnerability to kindling and associated comorbid ASD/ADHD-like behaviors.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalEpilepsy & Behavior
Volume65
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

Keywords

  • Brain morphology
  • Epilepsy
  • Kindling susceptibility
  • Neurodevelopmental disorders
  • White matter

Cite this

Sharma, Pragati ; Dedeurwaerdere, Stefanie ; Vandenberg, Michael A.D. ; Fang, Ke ; Johnston, Leigh A. ; Shultz, Sandy R. ; O'Brien, Terence J. ; Gilby, Krista L. / Neuroanatomical differences in FAST and SLOW rat strains with differential vulnerability to kindling and behavioral comorbidities. In: Epilepsy & Behavior. 2016 ; Vol. 65. pp. 42-48.
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abstract = "Objective The neurobiological factors underlying a predisposition towards developing epilepsy and its common behavioral comorbidities are poorly understood. FAST rats are a strain that has been selectively bred for enhanced vulnerability to kindling, while the SLOW strain has been bred to be resistant to kindling. FAST rats also exhibit behavioral traits reminiscent of those observed in neurodevelopmental disorders (autism spectrum disorder (ASD)/attention-deficit/hyperactivity disorder (ADHD)) commonly comorbid with epilepsy. In this study, we aimed to investigate neuroanatomical differences between these strains that may be associated with a differential vulnerability towards these interrelated disorders. Methods Ex vivo high-resolution magnetic resonance imaging on adult male FAST and SLOW rat brains was performed to identify morphological differences in regions of interest between the two strains. Behavioral examination using open-field, water consumption, and restraint tests was also conducted on a subgroup of these rats to document their differential ASD/ADHD-like behavior phenotype. Using optical stereological methods, the volume of cerebellar granule, white matter, and molecular layer and number of Purkinje cells were compared in a separate cohort of adult FAST and SLOW rats. Results Behavioral testing demonstrated hyperactivity, impulsivity, and polydipsia in FAST versus SLOW rats, consistent with an ASD/ADHD-like phenotype. Magnetic resonance imaging analysis identified brain structural differences in FAST compared with SLOW rats, including increased volume of the cerebrum, corpus callosum, third ventricle, and posterior inferior cerebellum, while decreased volume of the anterior cerebellar vermis. Stereological measurements on histological slices indicated significantly larger white matter layer volume, reduced number of Purkinje cells, and smaller molecular layer volume in the cerebellum in FAST versus SLOW rats. Significance These findings provide evidence of structural differences between the brains of FAST and SLOW rats that may be mechanistically related to their differential vulnerability to kindling and associated comorbid ASD/ADHD-like behaviors.",
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Neuroanatomical differences in FAST and SLOW rat strains with differential vulnerability to kindling and behavioral comorbidities. / Sharma, Pragati; Dedeurwaerdere, Stefanie; Vandenberg, Michael A.D.; Fang, Ke; Johnston, Leigh A.; Shultz, Sandy R.; O'Brien, Terence J.; Gilby, Krista L.

In: Epilepsy & Behavior, Vol. 65, 01.12.2016, p. 42-48.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Neuroanatomical differences in FAST and SLOW rat strains with differential vulnerability to kindling and behavioral comorbidities

AU - Sharma, Pragati

AU - Dedeurwaerdere, Stefanie

AU - Vandenberg, Michael A.D.

AU - Fang, Ke

AU - Johnston, Leigh A.

AU - Shultz, Sandy R.

AU - O'Brien, Terence J.

AU - Gilby, Krista L.

PY - 2016/12/1

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N2 - Objective The neurobiological factors underlying a predisposition towards developing epilepsy and its common behavioral comorbidities are poorly understood. FAST rats are a strain that has been selectively bred for enhanced vulnerability to kindling, while the SLOW strain has been bred to be resistant to kindling. FAST rats also exhibit behavioral traits reminiscent of those observed in neurodevelopmental disorders (autism spectrum disorder (ASD)/attention-deficit/hyperactivity disorder (ADHD)) commonly comorbid with epilepsy. In this study, we aimed to investigate neuroanatomical differences between these strains that may be associated with a differential vulnerability towards these interrelated disorders. Methods Ex vivo high-resolution magnetic resonance imaging on adult male FAST and SLOW rat brains was performed to identify morphological differences in regions of interest between the two strains. Behavioral examination using open-field, water consumption, and restraint tests was also conducted on a subgroup of these rats to document their differential ASD/ADHD-like behavior phenotype. Using optical stereological methods, the volume of cerebellar granule, white matter, and molecular layer and number of Purkinje cells were compared in a separate cohort of adult FAST and SLOW rats. Results Behavioral testing demonstrated hyperactivity, impulsivity, and polydipsia in FAST versus SLOW rats, consistent with an ASD/ADHD-like phenotype. Magnetic resonance imaging analysis identified brain structural differences in FAST compared with SLOW rats, including increased volume of the cerebrum, corpus callosum, third ventricle, and posterior inferior cerebellum, while decreased volume of the anterior cerebellar vermis. Stereological measurements on histological slices indicated significantly larger white matter layer volume, reduced number of Purkinje cells, and smaller molecular layer volume in the cerebellum in FAST versus SLOW rats. Significance These findings provide evidence of structural differences between the brains of FAST and SLOW rats that may be mechanistically related to their differential vulnerability to kindling and associated comorbid ASD/ADHD-like behaviors.

AB - Objective The neurobiological factors underlying a predisposition towards developing epilepsy and its common behavioral comorbidities are poorly understood. FAST rats are a strain that has been selectively bred for enhanced vulnerability to kindling, while the SLOW strain has been bred to be resistant to kindling. FAST rats also exhibit behavioral traits reminiscent of those observed in neurodevelopmental disorders (autism spectrum disorder (ASD)/attention-deficit/hyperactivity disorder (ADHD)) commonly comorbid with epilepsy. In this study, we aimed to investigate neuroanatomical differences between these strains that may be associated with a differential vulnerability towards these interrelated disorders. Methods Ex vivo high-resolution magnetic resonance imaging on adult male FAST and SLOW rat brains was performed to identify morphological differences in regions of interest between the two strains. Behavioral examination using open-field, water consumption, and restraint tests was also conducted on a subgroup of these rats to document their differential ASD/ADHD-like behavior phenotype. Using optical stereological methods, the volume of cerebellar granule, white matter, and molecular layer and number of Purkinje cells were compared in a separate cohort of adult FAST and SLOW rats. Results Behavioral testing demonstrated hyperactivity, impulsivity, and polydipsia in FAST versus SLOW rats, consistent with an ASD/ADHD-like phenotype. Magnetic resonance imaging analysis identified brain structural differences in FAST compared with SLOW rats, including increased volume of the cerebrum, corpus callosum, third ventricle, and posterior inferior cerebellum, while decreased volume of the anterior cerebellar vermis. Stereological measurements on histological slices indicated significantly larger white matter layer volume, reduced number of Purkinje cells, and smaller molecular layer volume in the cerebellum in FAST versus SLOW rats. Significance These findings provide evidence of structural differences between the brains of FAST and SLOW rats that may be mechanistically related to their differential vulnerability to kindling and associated comorbid ASD/ADHD-like behaviors.

KW - Brain morphology

KW - Epilepsy

KW - Kindling susceptibility

KW - Neurodevelopmental disorders

KW - White matter

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