Prenatal alcohol exposure differently affects seizure susceptibility and severity depending on its mechanism of induction: role of excitatory synapses and parvalbumin-positive interneurons.
Source: PubMed, NCBI / U.S. National Library of Medicine
Prenatal alcohol exposure (PAE) leads to several neurological developmental deficits, including seizure predisposition. It is speculated that alcohol would interfere with the development of GABAergic neurons, which would fail to control neocortical excitability. In order to test this hypothesis, we have orally exposed pregnant Swiss mice to 3 g/kg of ethanol or water daily from gestational day (G)14 until G19. At post-natal day (P)16, their offspring were submitted to analysis of seizure susceptibility and severity either by 80 mg/kg of pentylenetetrazol- or hyperthermia-provoked seizures. Subsequently, animals were euthanized and brains fixed and harvested for anatomical and immunofluorescent analyses of the number and distribution of vGluT1, parvalbumin (PV), somatostatin (SST) or vasointestinal peptide (VIP)-positive interneurons in the somatosensory cortex. We have found that PAE differently modulates seizures, depending on its induction mechanism: it promoted increased seizure severity after PTZ induction, but decreased seizure susceptibility after hyperthermia. Anatomical analyses revealed no alteration of cortical size. Immunofluorescence showed that PV+, but not SST+ and VIP+ interneurons, are increased in number in the somatosensory cortex, mainly in the supragranular layers. Besides, vGlut1-positive presynaptic sites were increased after PAE. These results suggest that PAE promotes increased presence of PV+ interneurons in the somatosensory neocortex,
Abstract
Prenatal alcohol exposure (PAE) leads to several neurological developmental deficits, including seizure predisposition. It is speculated that alcohol would interfere with the development of GABAergic neurons, which would fail to control neocortical excitability. In order to test this hypothesis, we have orally exposed pregnant Swiss mice to 3 g/kg of ethanol or water daily from gestational day (G)14 until G19. At post-natal day (P)16, their offspring were submitted to analysis of seizure susceptibility and severity either by 80 mg/kg of pentylenetetrazol- or hyperthermia-provoked seizures. Subsequently, animals were euthanized and brains fixed and harvested for anatomical and immunofluorescent analyses of the number and distribution of vGluT1, parvalbumin (PV), somatostatin (SST) or vasointestinal peptide (VIP)-positive interneurons in the somatosensory cortex. We have found that PAE differently modulates seizures, depending on its induction mechanism: it promoted increased seizure severity after PTZ induction, but decreased seizure susceptibility after hyperthermia. Anatomical analyses revealed no alteration of cortical size. Immunofluorescence showed that PV+, but not SST+ and VIP+ interneurons, are increased in number in the somatosensory cortex, mainly in the supragranular layers. Besides, vGlut1-positive presynaptic sites were increased after PAE. These results suggest that PAE promotes increased presence of PV+ interneurons in the somatosensory neocortex, which in turn, may promote a homeostatic enhancement of excitatory circuitry to maintain E/I balance. When PTZ blocks GABAA receptors, it unmasks this enhanced excitatory circuitry, increasing seizure severity. On the other hand, when submitted to hyperthermia, the increased PV+ network protects from seizure generation, decreasing its susceptibility.