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Differences in white matter structure between seizure prone (FAST) and seizure resistant (SLOW) rat strains
Copyright policy )Differences in white matter structure between seizure prone (FAST) and seizure resistant (SLOW) rat strains
Alterations in white matter integrity have been well documented in chronic epilepsy and during epileptogenesis. However, the relationship between white matter integrity and a predisposition towards epileptogenesis has been understudied. The FAST rat strain exhibit heightened susceptibility towards kindling epileptogenesis whereas SLOW rats are highly resistant. FAST rats also display behavioral phenotypes reminiscent of those observed in neurodevelopmental disorders that commonly comorbid with epilepsy. In this study, we aim to identify differences in white matter integrity that may contribute to a predisposition towards epileptogenesis and its associated comorbidities in 6 month old FAST (n = 10) and SLOW (n = 10) male rats. Open field and water consumption tests were conducted to confirm the behavioral phenotype difference between FAST and SLOW rats followed by ex-vivo diffusion-weighted magnetic resonance imaging to identify differences in white matter integrity. Diffusion tensor imaging scalar values namely fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were compared in the anterior commissure, corpus callosum, external capsule, internal capsule, fimbria and optic tract. Electron microscopy was used to evaluate microstructural alterations in myelinated axons. Behavioral phenotyping confirmed higher activity levels (distance moved on days 2–4, p < 0.001; number of rearings on days 2 and 4, p < 0.05 at both days) and polydipsia (p < 0.001) in FAST rats. Comparative analysis of diffusion tensor imaging scalars found a significant decrease in fractional anisotropy in the corpus callosum (p < 0.05) of FAST versus SLOW rats. Using electron microscopy, alterations in myelinated axons including increased axon diameter (p < 0.001) and reduced g-ratio (p < 0.001) in the midline of the corpus callosum in 6 month old FAST (n = 3) versus SLOW (n = 4) male rats. These findings suggest that differences in white matter integrity between FAST and SLOW rats could be a contributing factor to the differential seizure susceptibility and behavioral phenotypes observed in these strains.
- University of Melbourne Australia
- Florey Institute of Neuroscience and Mental Health Australia
Microsoft Academic Graph classification: Pathology medicine.medical_specialty Internal capsule External capsule Anterior commissure Biology Corpus callosum Epileptogenesis White matter Fractional anisotropy medicine medicine.anatomical_structure Diffusion MRI
Library of Congress Subject Headings: lcsh:RC321-571 lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Male, Drinking, Cohort Studies, Seizures, Image Processing, Computer-Assisted, Animals, Myelin Sheath, Analysis of Variance, Epilepsy, Neurodevelopmental disorders, White Matter, Electric Stimulation, Rats, Disease Models, Animal, Diffusion Tensor Imaging, Neurology, Exploratory Behavior, Anisotropy, Locomotion, Seizure susceptibility
Male, Drinking, Cohort Studies, Seizures, Image Processing, Computer-Assisted, Animals, Myelin Sheath, Analysis of Variance, Epilepsy, Neurodevelopmental disorders, White Matter, Electric Stimulation, Rats, Disease Models, Animal, Diffusion Tensor Imaging, Neurology, Exploratory Behavior, Anisotropy, Locomotion, Seizure susceptibility
Microsoft Academic Graph classification: Pathology medicine.medical_specialty Internal capsule External capsule Anterior commissure Biology Corpus callosum Epileptogenesis White matter Fractional anisotropy medicine medicine.anatomical_structure Diffusion MRI
Library of Congress Subject Headings: lcsh:RC321-571 lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
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Citations provided by BIP!Popularity provided by BIP!- National Health and Medical Research Council (NHMRC) (NHMRC)
- 1082215
- Project Grants
- University of Melbourne Australia
- Florey Institute of Neuroscience and Mental Health Australia
Alterations in white matter integrity have been well documented in chronic epilepsy and during epileptogenesis. However, the relationship between white matter integrity and a predisposition towards epileptogenesis has been understudied. The FAST rat strain exhibit heightened susceptibility towards kindling epileptogenesis whereas SLOW rats are highly resistant. FAST rats also display behavioral phenotypes reminiscent of those observed in neurodevelopmental disorders that commonly comorbid with epilepsy. In this study, we aim to identify differences in white matter integrity that may contribute to a predisposition towards epileptogenesis and its associated comorbidities in 6 month old FAST (n = 10) and SLOW (n = 10) male rats. Open field and water consumption tests were conducted to confirm the behavioral phenotype difference between FAST and SLOW rats followed by ex-vivo diffusion-weighted magnetic resonance imaging to identify differences in white matter integrity. Diffusion tensor imaging scalar values namely fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were compared in the anterior commissure, corpus callosum, external capsule, internal capsule, fimbria and optic tract. Electron microscopy was used to evaluate microstructural alterations in myelinated axons. Behavioral phenotyping confirmed higher activity levels (distance moved on days 2–4, p < 0.001; number of rearings on days 2 and 4, p < 0.05 at both days) and polydipsia (p < 0.001) in FAST rats. Comparative analysis of diffusion tensor imaging scalars found a significant decrease in fractional anisotropy in the corpus callosum (p < 0.05) of FAST versus SLOW rats. Using electron microscopy, alterations in myelinated axons including increased axon diameter (p < 0.001) and reduced g-ratio (p < 0.001) in the midline of the corpus callosum in 6 month old FAST (n = 3) versus SLOW (n = 4) male rats. These findings suggest that differences in white matter integrity between FAST and SLOW rats could be a contributing factor to the differential seizure susceptibility and behavioral phenotypes observed in these strains.