Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits after Pediatric Traumatic Brain Injury

Lengel, Dana; Romm, Zoe; Bostwick, Anna; Huh, Jimmy W.; Snyder, Nathaniel W.; Smith, George M.; Raghupathi, Ramesh

doi:10.1089/neu.2022.0012

Cited by 12 publications

(10 citation statements)

References 62 publications

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“…A straightforward prediction, thus, is that GR loss might reduce neuronal activity within the hippocampus such that firing is sufficient only to sustain more focal seizures, but not to robustly recruit extrahippocampal structures. Alternatively, GRs can regulate long-term potentiation ( Lengel et al, 2022 ), and potentiation of granule cell – mossy cell synapses has been shown to increase SE severity following kainic acid treatment ( Nasrallah et al, 2022 ). Indeed, GR knockdown in the present study occurred in neurons (dentate, CA1, CA3) participating in the three key synapses of the classic hippocampal trisynaptic circuit, and altered synaptic strength or plasticity at any (or all) of these could reduce hippocampal output.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal glucocorticoid receptors modulate status epilepticus severity

Kraus

Nawreen

Godale

et al. 2023

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Hippocampal glucocorticoid receptors modulate status epilepticus severity

Kraus

Nawreen

Godale

et al. 2023

Neurobiology of Disease

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“…In the selection process of GR signal regulated thymocytes, mitochondria can act as an important signal-integrator organelles [18]. Interestingly, GR signaling plays an important regulatory role in hippocampal selection and apoptosis [68]. When GCs bind to their receptor, GR is isolated from Hsp-90 and translocated to the nucleus, where it binds to the target genes and acts as a transcription factor [69].…”

Section: Discussionmentioning

confidence: 99%

Icariin prevents depression-like behaviors in chronic unpredictable mild stress-induced rats through Bax/cytoplasm C/caspase-3 axis to alleviate neuronal apoptosis

Zhang

Sun

et al. 2023

Preprint

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Major depressive disorder (MDD) affects approximately 16% of the global population. Our previous study has demonstrated that icariin (ICA) exhibits anti-depressant activity by increasing the expression of Brain Derived Neurotrophic Factor (BDNF) in a rat model of chronic unpredictable mild stress (CUMS). In this study, we investigated whether and how ICA can prevent CUMS-induced depression-like behaviors in rats by modulating hippocampus neuronal apoptosis. Forty male rats were randomly divided into control, CUMS, CUMS-fluoxetine (Flx) (10 mg/kg), and CUMS-ICA (20 mg/kg) groups. Behavior tests including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM), and forced swimming tests (FST) were performed. The Nissl staining and TUNNEL assay were used to determine neuronal apoptosis. Subsequently, expression of glucocorticoid receptor (GR), Bcl-2, cytochrome C, caspase-3 and Bax in the hippocampus were tested by western blot . Our results show that a chronic administration of ICA (20 mg/kg) can prevent CUMS-induced depressant-like behaviors in male model rats. Additionally, ICA significantly inhibited mitochondrial translocation of GR, reduced mitochondrial outer membrane permeabilization (MOMP) to suppress the release of cytochrome C, and then inhibit the activation of caspase-3. In conclusion, our research provides new evidence to understand the anti-depressant activity of ICA, which relates to its inhibition of neuronal apoptosis in hippocampus through mitochondrial apoptotic pathway.

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“…Reduced neurological deficits and brain water content; Multiple HBO sessions/ day were more protective than a single session Gene therapy FPI 112 Rat (#) 20 min post-TBI; VEGF-ZFP Functional recovery; reduced apoptosis; increased microvascular density and diameter CCI 114 Juvenile rat (# & $) 7 days post-TBI; human GR Improved spatial learning and memory CCI 115 Mouse (#) Soon after TBI; ski Reduced lesion volume and astrogliosis; Improved neurological recovery; promoted neurogenesis Weight-drop 113 Rat (#) 15 min post-TBI; IGF-1 Reduced oxidative stress & cognitive deficits Dietary adaptation CCI 57 Rat (#) Pre-and post-TBI 30% CR Improved spatial learning and memory Reduced lesion volume; upregulation of BDNF expression CCI 65 Juvenile rat (#) Post-TBI KD for 7 days Reduced cortical contusion volume at PND35 and PND45, but not PND17 and PND65…”

Section: Hyperbaric Oxygenmentioning

confidence: 99%

Non-pharmacological interventions for traumatic brain injury

Davis,

Arruri,

Joshi

et al. 2024

J Cereb Blood Flow Metab

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Heterogeneity and variability of symptoms due to the type, site, age, sex, and severity of injury make each case of traumatic brain injury (TBI) unique. Considering this, a universal treatment strategy may not be fruitful in managing outcomes after TBI. Most of the pharmacological therapies for TBI aim at modifying a particular pathway or molecular process in the sequelae of secondary injury rather than a holistic approach. On the other hand, non-pharmacological interventions such as hypothermia, hyperbaric oxygen, preconditioning with dietary adaptations, exercise, environmental enrichment, deep brain stimulation, decompressive craniectomy, probiotic use, gene therapy, music therapy, and stem cell therapy can promote healing by modulating multiple neuroprotective mechanisms. In this review, we discussed the major non-pharmacological interventions that are being tested in animal models of TBI as well as in clinical trials. We evaluated the functional outcomes of various interventions with an emphasis on the links between molecular mechanisms and outcomes after TBI.

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Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits after Pediatric Traumatic Brain Injury

Cited by 12 publications

References 62 publications

Hippocampal glucocorticoid receptors modulate status epilepticus severity

Hippocampal glucocorticoid receptors modulate status epilepticus severity

Icariin prevents depression-like behaviors in chronic unpredictable mild stress-induced rats through Bax/cytoplasm C/caspase-3 axis to alleviate neuronal apoptosis

Non-pharmacological interventions for traumatic brain injury

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