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

Delayed myelination and neurodevelopment in male seizure‐prone versus seizure‐resistant rats

“…Interestingly, locomotor activity levels proved to be lower in FAST pups throughout the preweaning period despite weight and neuromuscular (grip strength) equivalencies. This finding is in contrast to the many experiments demonstrating relative hyperactivity in FAST versus SLOW rats from young adulthood onward . Important to the clinical relevance of this finding is that a PND 20 rat matches a human age of only 8 months, a time point when the corresponding locomotor activity would not yet be measurable in humans.…”

“…FAST rats also display a behavioral phenotype reminiscent of neurodevelopmental disorders that are comorbid with epilepsy, namely autism spectrum disorder (ASD) and attention‐deficit/hyperactivity disorder (ADHD) . Furthermore, and of relevance to this study, our recent magnetic resonance imaging and diffusion tensor imaging studies demonstrated white matter structural and volume differences in the corpus callosum and the cerebellum between FAST and SLOW adult rats . In light of this finding, and because investigation into myelination in developmentally delayed children has largely focused on the cortex or subcortical regions such as the brainstem and the cerebellum, in this study myelination was compared in these structures by way of myelin‐specific gene and protein expression at various postnatal developmental time points.…”

“…This finding is in contrast to the many experiments demonstrating relative hyperactivity in FAST versus SLOW rats from young adulthood onward. [12][13][14] Important to the clinical relevance of this finding is that a PND 20 rat matches a human age of only 8 months, a time point when the corresponding locomotor activity would not yet be measurable in humans.…”

“…12 Furthermore, and of relevance to this study, our recent magnetic resonance imaging and diffusion tensor imaging studies demonstrated white matter structural and volume differences in the corpus callosum and the cerebellum between FAST and SLOW adult rats. 13,14 In light of this finding, and because investigation into myelination in developmentally delayed children has largely focused on the cortex or subcortical regions such as the brainstem 15 and the cerebellum, 16 in this study myelination was compared in these structures by way of myelin-specific gene and protein expression at various postnatal developmental time points. The 4 principle myelin components examined are involved in both formation and structural integrity of the myelin sheath, namely myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein (MOG).…”

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

“…Behaviorally, the FAST rats appear much like humans with attention deficit hyperactivity disorder (ADHD), showing easy distraction, hyperactivity and impulsivity, compared to SLOW rats. More recently, Sharma et al [43] aimed to investigate neuroanatomical differences between these strains that may be associated with a differential vulnerability towards kindling and behavioral comorbidities. Behavioral testing demonstrated hyperactivity, impulsivity, and polydipsia differences in FAST versus SLOW rats, consistent with an ASD (autism spectrum disorder)/ADHD-like phenotype.…”