Early Life Febrile Seizures Impair Hippocampal Synaptic Plasticity in Young Rats

Autor: Dmitry V. Amakhin, Alexandra V. Griflyuk, Olga E. Zubareva, Aleksey V. Zaitsev, Elena B. Soboleva, Anna A. Kovalenko, Tatyana Y. Postnikova
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 15
International Journal of Molecular Sciences, Vol 22, Iss 8218, p 8218 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22158218
Popis: 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.
Databáze: OpenAIRE
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