Early Life Febrile Seizures Impair Hippocampal Synaptic Plasticity in Young Rats.

Tatyana Y Postnikova,Alexandra V Griflyuk,Anna A Kovalenko,Aleksey V Zaitsev,Dmitry V Amakhin,Elena B Soboleva,Olga E Zubareva

doi:10.3390/ijms22158218

Abstract

Febrile seizures (FSs) in early life are significant risk factors of neurological disorders and cognitive impairment in later life. However, existing data about the impact of FSs on the developing brain are conflicting. We aimed to investigate morphological and functional changes in the hippocampus of young rats exposed to hyperthermia-induced seizures at postnatal day 10. We found that FSs led to a slight morphological disturbance. The cell numbers decreased by 10% in the CA1 and hilus but did not reduce in the CA3 or dentate gyrus areas. In contrast, functional impairments were robust. Long-term potentiation (LTP) in CA3-CA1 synapses was strongly reduced, which we attribute to the insufficient activity of N-methyl-D-aspartate receptors (NMDARs). Using whole-cell recordings, we found higher desensitization of NMDAR currents in the FS group. Since the desensitization of NMDARs depends on subunit composition, we analyzed NMDAR current decays and gene expression of subunits, which revealed no differences between control and FS rats. We suggest that an increased desensitization is due to insufficient activation of the glycine site of NMDARs, as the application of D-serine, the glycine site agonist, allows the restoration of LTP to a control value. Our results reveal a new molecular mechanism of FS impact on the developing brain.

Highlights

Infectious diseases with fever can provoke febrile seizures (FSs) [1,2], which constitute one of the most common neurological disorders in children between 3 months and 5 years [3]
FSs in early life may lead to sustained dysfunction of hippocampal neurons without cell death [19,20]
The results suggest that changes in the subunit composition of N-methyl-D-aspartate receptors (NMDARs) and AMPARs are not likely to occur in this model of febrile seizures

Summary

Introduction

Infectious diseases with fever can provoke febrile seizures (FSs) [1,2], which constitute one of the most common neurological disorders in children between 3 months and 5 years [3]. FSs are divided into simple FSs (lasting < 10–15 min) and complex FSs (lasting >15 min) [4,5]. This classification is currently accepted as having predictive value. Clinical studies have shown that adults who experienced more prolonged FSs in early life frequently demonstrate a broad range of neurological disorders in later life [7,8,9]. As with many other negative factors acting in early life, the FSs can cause long-lasting alteration of cognitive functions, learning and memory [10,11,12,13,14]

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