Progesterone treatment following traumatic brain injury in the 11-day-old rat attenuates cognitive deficits and neuronal hyperexcitability in adolescence.

Autor: Lengel D; Program in Neuroscience, Graduate School of Biomedical Sciences and Professional Studies, Drexel University College of Medicine, Philadelphia, PA United States of America., Huh JW; Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America., Barson JR; Program in Neuroscience, Graduate School of Biomedical Sciences and Professional Studies, Drexel University College of Medicine, Philadelphia, PA United States of America; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United States of America., Raghupathi R; Program in Neuroscience, Graduate School of Biomedical Sciences and Professional Studies, Drexel University College of Medicine, Philadelphia, PA United States of America; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United States of America. Electronic address: rr79@drexel.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2020 Aug; Vol. 330, pp. 113329. Date of Electronic Publication: 2020 Apr 23.
DOI: 10.1016/j.expneurol.2020.113329
Abstrakt: Traumatic brain injury (TBI) in children younger than 4 years old results in cognitive and psychosocial deficits in adolescence and adulthood. At 4 weeks following closed head injury on postnatal day 11, male and female rats exhibited impairment in novel object recognition memory (NOR) along with an increase in open arm time in the elevated plus maze (EPM), suggestive of risk-taking behaviors. This was accompanied by an increase in intrinsic excitability and frequency of spontaneous excitatory post-synaptic currents (EPSCs), and a decrease in the frequency of spontaneous inhibitory post-synaptic currents in layer 2/3 neurons within the medial prefrontal cortex (PFC), a region that is implicated in both object recognition and risk-taking behaviors. Treatment with progesterone for the first week after brain injury improved NOR memory at the 4-week time point in both sham and brain-injured rats and additionally attenuated the injury-induced increase in the excitability of neurons and the frequency of spontaneous EPSCs. The effect of progesterone on cellular excitability changes after injury may be related to its ability to decrease the mRNA expression of the β3 subunit of the voltage-gated sodium channel and increase the expression of the neuronal excitatory amino acid transporter 3 in the medial PFC in sham- and brain-injured animals and also increase glutamic acid decarboxylase mRNA expression in sham- but not brain-injured animals. Progesterone treatment did not affect injury-induced changes in the EPM test. These results demonstrate that administration of progesterone immediately after TBI in 11-day-old rats reduces cognitive deficits in adolescence, which may be mediated by progesterone-mediated regulation of excitatory signaling mechanisms within the medial PFC.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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