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Delayed myelination and neurodevelopment in male seizure‐prone versus seizure‐resistant rats
Author(s) -
Sharma Pragati,
Powell Kim L.,
Wlodek Mary E.,
O'Brien Terence J.,
Gilby Krista L.
Publication year - 2018
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14013
Subject(s) - brainstem , righting reflex , epilepsy , epileptogenesis , cerebellum , myelin , neuroscience , endocrinology , psychology , medicine , central nervous system , anesthesia , biology , reflex
Summary Objective Aberrant myelination and developmental delay have been reported in epilepsy. However, it is unclear whether these are linked to intrinsic mechanisms that support a predisposition toward seizures and the development of epilepsy. Thus, we compared rates of myelination and neurodevelopment in male rats selectively bred for enhanced susceptibility to kindling epileptogenesis ( FAST ) with male rats bred for resistance ( SLOW ). Methods Myelin‐specific gene expression was compared in the brainstem, cerebellum, and cerebral hemisphere of FAST and SLOW rats on postnatal days ( PNDs ) 5, 11, 17, 23, and 90 to determine strain‐specific myelination rates. Myelin protein levels were also compared at PND s 5 and 23 in the brainstem. Relative rates of neurodevelopment were evaluated between PND s 5 and 21 using physical growth landmarks and neuromotor tests including righting reflex, cliff avoidance, negative geotaxis, and locomotor activity. Results Myelin‐specific mRNA expression was significantly down‐regulated in FAST rats on PND s 5 and 11 in all 3 brain structures, indicating relatively delayed myelination. Likewise, corresponding protein levels were significantly lower in FAST brainstem on PND 5. Developmental delay was evident in the FAST strain such that only 9% of FAST pups, compared to 81% of SLOW , had open eyes by PND 13, locomotor activity was significantly reduced between PND s 12 and 16, and neuromotor task acquisition was delayed between PND s 5 and 10. Significance Relative delays in myelination and neurodevelopment co‐occurred in the seizure‐prone FAST strain in the absence of seizures. These findings suggest these symptoms are not seizure‐induced and may be mechanistically linked to an underlying pathophysiology supporting a predisposition toward developing epilepsy.