Maternal Hypoxia Increases the Excitability of Neurons in the Entorhinal Cortex and Dorsal Hippocampus of Rat Offspring

Abstract

Prenatal hypoxia is a widespread condition that causes various disturbances in later life, including aberrant central nervous system development, abnormalities in EEG rhythms, and susceptibility to seizures. Hypoxia in rats on the 14th day of embryogenesis (E14) disrupts cortical neuroblast radial migration, mainly affecting the progenitors of cortical glutamatergic neurons but not GABAergic interneurons or hippocampal neurons. Thus, hypoxia at this time point might affect the development of the neocortex to a greater extent than the hippocampus. In the present study, we investigated the long-term effects of hypoxia on the properties of the pyramidal neurons in the hippocampus and entorhinal cortex (EC) in 3-week-old rats subjected to hypoxia on E14. We observed a reduction in the total number of NeuN-positive neurons in EC but not in the CA1 field of the hippocampus, indicating an increased cell loss in EC. However, the principal neuron electrophysiological characteristics were altered in the EC and hippocampus of animals exposed to hypoxia. The whole-cell patch-clamp recordings revealed a similar increase in input resistance in neurons from the hippocampus and EC. However, the resting membrane potential was increased in the EC neurons only. The recordings of field postsynaptic potentials (fPSPs) in the CA1 hippocampal area showed that both the threshold currents inducing fPSPs and population spikes were lower in hypoxic animals compared to age-matched controls. Using the dosed electroshock paradigm, we found that seizure thresholds were lower in the hypoxic group. Thus, the obtained results suggest that maternal hypoxia during the generation of the pyramidal cortical neurons leads to the increased excitability of neuronal circuitries in the brain of young rats. The increased excitability can be attributed to the changes in intrinsic neuronal properties.

Oxidative stress accompanies HIF1-dependent impairment of glucose metabolism in the hippocampus of adult rats survived prenatal severe hypoxia

“…Epigenetic programming during fetal development is a very important and complexly organized process that determines the balance of gene expression speci c to cells and tissues and determines a plasticity during their life and adaptation to permanently changing environmental conditions [28,51]. The impact of stressors (e.g., hypoxic stress) during the period of HPC maturation not only has a direct damaging effect on a fetus [25,52], but also can cause intracellular processes, which are stable throughout life, associated with a steady change in the patterns of epigenetic modi cations [18,26,53]. A signi cant increase in the levels of HIF1α protein in the brain of a 21-day-old fetus was previously shown on a model of antenatal hypoxia [10], which indicated a hypoxic condition in the fetal brain tissues.…”