Abstract
BackgroundMaternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring.MethodsForty timed-pregnant Wistar rats were divided into four groups: A) Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy) rats that received repeated intraperitoneal (i.p.) pentylenetetrazol, PTZ injections on gestational days (GD) 14-19; B) Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C) Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D) Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry.ResultsOur data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001) and Kind-/Seiz+ (p = 0.001) groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007) and Kind-/Seiz+ (p = 0.007) group’s newborns on both PD1 and 14.ConclusionOur findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.
Highlights
Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring
Development of hippocampus initiates from embryonic day 13 (E13), and E14-E20 is a critical period for neurogenesis and neural migration in the hippocampus [12,34,35]
Because hippocampal development normally continues until two weeks after birth in rat pups, we evaluated the effect of maternal epileptic seizures on PSANCAM expression in rat pups hippocampi on Postnatal Day (PD) 1 and 14
Summary
Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. PSA-NCAM is highly expressed in developing and migrating neurons especially during prenatal and early-postnatal neurodevelopment [18,19]. This molecule plays a critical role in neural plasticity, axonal outgrowth, neurogenesis, synaptogenesis; and in several phenomena such as recognition, learning, and spatial memory [16,20,21]. Elimination of PSA causes impairment in neural cell migration, neurite sprouting, synaptogenesis, and learning/memory [22,23,24]
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