Changes in synaptic AMPA receptor concentration and composition in chronic temporal lobe epilepsy

Egbenya, Daniel Lawer; Hussain, Suleman; Lai, Yi‐Chen; Xia, Jun; Anderson, Anne E.; Davanger, Svend

doi:10.1016/j.mcn.2018.07.004

Cited by 36 publications

(35 citation statements)

References 45 publications

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“…At the same time, pregnenolone sulfate as well as conjugated pregnanolone are inhibitory and neuroprotective for another type of glutamate receptors, the AMPA/kainate (AMPAR/KAR) receptors [98] (Table 6). AMPAR/KAR receptor overactivation and/or changes in receptor subunits may induce excitotoxic neuronal damage or death [99] in various neurological diseases [100,101]. As previously demonstrated by Wang et al [81], the influx of peripheral pregnenolone sulfate across the blood-brain barrier in a rat model was evident.…”

Section: Progestogensmentioning

confidence: 71%

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

Honců

Hill

Bičı́ková

et al. 2019

IJMS

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Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland’s role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.

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Section: Progestogensmentioning

confidence: 71%

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

Honců

Hill

Bičı́ková

et al. 2019

IJMS

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“…However, expression level of AMPAR subunits are decreased in the epileptic hippocampus of animal models [6]. Furthermore, the concentration of the whole hippocampal synaptosomal GRIA1 is reduced in chronic epilepsy rats [18]. Therefore, it has been still elusive how AMPAR is involved in the seizure onset and neuronal hyperexcitability in the epileptic hippocampus.…”

Section: Discussionmentioning

confidence: 99%

PTEN Is Required for The Anti-Epileptic Effects of AMPA Receptor Antagonists in Chronic Epileptic Rats

Kim

Park

Lee

et al. 2020

IJMS

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α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is one of the ligand-gated ion channels for glutamate, which is an important player in the generation and spread of seizures. The efficacy of AMPAR functionality is regulated by the trafficking, synaptic targeting, and phosphorylation. Paradoxically, AMPAR expression and its phosphorylation level are decreased in the epileptic hippocampus. Therefore, the roles of AMPAR in seizure onset and neuronal hyperexcitability in ictogenesis remain to be elucidated. In the present study, we found that AMPAR antagonists (perampanel and GYKI 52466) decreased glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) surface expression in the epileptic rat hippocampus. They also upregulated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression and restored to basal levels the upregulated phosphoinositide 3-kinase (PI3K)/AKT1 phosphorylations. Dipotassium bisperoxovanadium(pic) dihydrate (BpV(pic), a PTEN inhibitor) co-treatment abolished the anti-epileptic effects of perampanel and GYKI 52466. Therefore, our findings suggest that PTEN may be required for the anti-epileptic effects of AMPAR antagonists.

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“…Importantly, application of patients' GluA2 antibodies in GluA1-knockout mice also led to reduced levels of AMPAR, but the replacement with GluA1-AMPARs of higher conductance was no longer present, suggesting that GluA1 homomeric receptors are responsible for the synaptic scaling-like mechanism observed in wild-type mice (95). Interestingly, recent studies showed that in rat models of chronic temporal lobe epilepsy there was a relative increase in inwardly rectifying non-GluA2 AMPARs, which was linked to neuronal excitotoxicity and seizure development (113,114). Determining whether the rearrangement of AMPAR subunits observed in the model of anti-AMPAR encephalitis results in increased neuronal excitability and enhanced seizure susceptibility is a goal of future studies.…”

Section: Paraneoplastic Encephalitismentioning

confidence: 99%

Autoimmune seizures and epilepsy

Geis

Planagumà

Carreño

et al. 2019

Journal of Clinical Investigation

169

149

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Changes in synaptic AMPA receptor concentration and composition in chronic temporal lobe epilepsy

Cited by 36 publications

References 45 publications

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

PTEN Is Required for The Anti-Epileptic Effects of AMPA Receptor Antagonists in Chronic Epileptic Rats

Autoimmune seizures and epilepsy

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