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

Lengel, Dana; Huh, Jimmy W.; Barson, Jessica R.; Raghupathi, Ramesh

doi:10.1016/j.expneurol.2020.113329

Cited by 19 publications

(20 citation statements)

References 81 publications

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“…Although evidence of neuronal death or neurodegeneration within the mPFC, has not been observed (Lengel et al, 2020), changes in dendritic morphology following TBI may be a potential mechanism underlying changes in the excitatory/inhibitory balance within the mPFC.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, our current data indicate that the effects of TBI on layer II/III IPSCs are sustained up to 7 weeks following injury. We previously identified changes in the excitatory amino acid transporter 3 (EAAT3) and voltage-gated sodium channel β3-subunit (NaVβ3) as potential mechanisms underlying the effects on cellular function by progesterone treatment during the first week following injury (Lengel et al, 2020). In the present study, because the OXT was administered 30 minutes prior to behavioral testing, it is more likely that its effects were mediated through acute changes in signal transduction, rather than transcriptional changes or anti-inflammatory effects of oxytocin.…”

Section: Discussionmentioning

confidence: 99%

“…The model of moderate pediatric TBI used in this study was originally characterized by Raghupathi and Huh (2007) and was subsequently used in multiple studies (Hanlon et al, 2017(Hanlon et al, , 2019Lengel et al, 2020). Animals from each litter were randomly assigned to sham-injury or brain-injury groups.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

“…OXT has been found to increase spontaneous inhibitory postsynaptic currents (IPSCs) and the release of gamma aminobutyric acid (GABA) (Wrobel et al, 2010;Harden and Frazier, 2016). We previously demonstrated that TBI in 11-day-old rats results in an increase in spontaneous excitatory postsynaptic currents (EPSCs) and a concomitant decrease in spontaneous IPSCs in layer II/III pyramidal neurons within the mPFC (Lengel et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…OXT has been found to increase spontaneous inhibitory postsynaptic currents (IPSCs) and the release of GABA ( Wrobel et al, 2010 ; Harden and Frazier, 2016 ). We previously demonstrated that TBI in 11-d-old rats results in an increase in spontaneous EPSCs and a concomitant decrease in spontaneous IPSCs in Layer II/III pyramidal neurons within the mPFC ( Lengel et al, 2020 ). Increasing excitatory currents in the PFC decreases social exploration in rodents ( Yizhar et al, 2011 ; Bicks et al, 2015 ), suggesting that changes in excitation/inhibition balance within the medial PFC may be a mechanism underlying deficits in social behaviors following TBI.…”

Section: Introductionmentioning

confidence: 99%

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Intranasal Administration of Oxytocin Attenuates Social Recognition Deficits and Increases Prefrontal Cortex Inhibitory Postsynaptic Currents following Traumatic Brain Injury

Runyan

Lengel

Huh

et al. 2021

eNeuro

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Pediatric traumatic brain injury (TBI) results in heightened risk for social deficits that can emerge during adolescence and adulthood. A moderate TBI in male and female rats on postnatal day 11 (equivalent to children below the age of 3) resulted in impairments in social novelty recognition, defined as the preference for interacting with a novel rat compared to a familiar rat, but not sociability, defined as the preference for interacting with a rat compared to an object in the three-chamber test when tested at 4-weeks (adolescence) and 8-weeks (adulthood) postinjury. The deficits in social recognition were not accompanied by deficits in novel object recognition memory and were associated with a decrease in the frequency of spontaneous inhibitory postsynaptic currents (IPSC) recorded from pyramidal neurons within layer II/III of the medial prefrontal cortex (mPFC). Whereas TBI did not affect the expression of oxytocin (OXT) or the oxytocin Receptor (OXT-R) mRNAs in the hypothalamus and mPFC respectively, intranasal administration of OXT prior to behavioral testing was found to reverse impairments in social novelty recognition and increase IPSC frequency in the mPFC in brain-injured animals.These results suggest that TBI-induced deficits in social behavior may be linked to increased excitability of neurons in the mPFC and suggests that the regulation of GABAergic neurotransmission in this region as a potential mechanism underlying these deficits. 3 Significance StatementTraumatic brain injury (TBI) occurs in approximately half a million children below the age of 14 each year, with children younger than 4 years old at heightened risk. A younger age at injury is associated with worse behavioral and psychosocial outcomes in pediatric TBI patients, particularly as children age into adolescence and adulthood. In this study, we explored the role of oxytocin in the long-term effects of pediatric TBI on social behaviors in adolescence and adulthood. The results indicate that intranasal administration of oxytocin (OXT) improves social outcomes following pediatric TBI, potentially by increasing inhibitory neurotransmission within the medial prefrontal cortex (mPFC) and provide novel support for the use of intranasal OXT treatment to mitigate social deficits in pediatric TBI patients.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Traumatic Brain Injurymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intranasal Administration of Oxytocin Attenuates Social Recognition Deficits and Increases Prefrontal Cortex Inhibitory Postsynaptic Currents following Traumatic Brain Injury

Runyan

Lengel

Huh

et al. 2021

eNeuro

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Defining Experimental Variability in Actuator-Driven Closed Head Impact in Rats

2022

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Environmental Enrichment Improves the Recognition Memory in Adult Mice Following Social Isolation via Downregulation of Kv4.2 Potassium Channels

Shang,

Dong,

et al. 2023

Mol Neurobiol

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The recognition memory is a cognitive process that enables us to distinguish familiar objects and situations from new items, which is essential for mammalian survival and adaptation to a changing environment. Social isolation (SI) has been implicated as a detrimental factor for recognition memory. The medial prefrontal cortex (mPFC) has been shown to carry information concerning the relative familiarity of individual stimuli, and modulating neuronal function in this region may contribute to recognition memory. The present study aimed to investigate the neuronal mechanisms in the mPFC of environmental enrichment (EE) on recognition memory in adult mice following SI. Mice were assigned into three groups: Control, SI, and SI + EE group. Novel location recognition (NLR) and Novel object recognition (NOR) tests were performed to evaluate the recognition memory. The levels of Kv4 channels were assessed by qRT-PCR and Western blotting. The effects of SI and SI + EE on the intrinsic excitability of pyramidal neurons in the mPFC were measured using whole-cell recording. We found that SI led to a reduction in the intrinsic excitability of pyramidal neurons. Speci cally, we have identi ed that the reduction in the ring activity of pyramidal neurons resulted from alterations in the function and expression of Kv4.2 channels. Furthermore, EE regulated Kv4.2 channels, normalized the activity of pyramidal neurons and restored the behavioral de cits following SI. Thus, the roles of Kv4.2 channels in intrinsic excitability of pyramidal neurons suggest that the Kv4.2 channels present a promising therapeutic target for recognition memory impairment.

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

Cited by 19 publications

References 81 publications

Intranasal Administration of Oxytocin Attenuates Social Recognition Deficits and Increases Prefrontal Cortex Inhibitory Postsynaptic Currents following Traumatic Brain Injury

Intranasal Administration of Oxytocin Attenuates Social Recognition Deficits and Increases Prefrontal Cortex Inhibitory Postsynaptic Currents following Traumatic Brain Injury

Defining Experimental Variability in Actuator-Driven Closed Head Impact in Rats

Environmental Enrichment Improves the Recognition Memory in Adult Mice Following Social Isolation via Downregulation of Kv4.2 Potassium Channels

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