Recurrent seizures cause immature brain injury and changes in GABA a receptor α1 and γ2 subunits

Xi, Xiao-Jun; Ji-hong, Tang; Zhang, Bingbing; Shi, Xiaoyan; Feng, Jun; Hu, Xiaoyue; Wan, Yu; Zhou, Cheng

doi:10.1016/j.eplepsyres.2020.106328

Cited by 6 publications

(5 citation statements)

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“…The different GABA A receptor subunits relatively contributed to the functional properties of the receptor by changing the channel function which causes changed receptor‐mediated fast inhibitory post‐synaptic potentials (Papatheodoropoulos et al, 2002). It has been demonstrated that the α1 subunit is one of the most found GABA A subunits which is associated with a learning deficit in epilepsy and mediates plasticity in context‐dependent learning (Xi et al, 2020). Also, GABA A receptors containing α5 subunit have mostly dendritic locations in the hippocampus regulating the dendritic excitability and thereby contributing to the neuronal plasticity underlying learning and memory processes.…”

Section: Discussionmentioning

confidence: 99%

“…The different GABA A receptor subunits relatively contributed to the functional properties of the receptor by changing the channel function which causes changed receptor-mediated fast inhibitory post-synaptic potentials (Papatheodoropoulos et al, 2002). It has been demonstrated that the α1 subunit is one of the most found GABA A subunits which is associated with a learning deficit in epilepsy and mediates plasticity in context-dependent learning (Xi et al, 2020).…”

Section: Rme Increases the Expression Of Gaba A Receptor α1 And α5 Su...mentioning

confidence: 99%

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A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

et al. 2022

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We aimed to study how morphine affects synaptic transmission in the dentate gyrus and CA1 regions along the hippocampal long axis. For this, recording and measuring of field excitatory postsynaptic potentials (fEPSPs) were utilized to test the effects of repeated morphine exposure on paired-pulse evoked responses and long-term potentiation (LTP) at Schaffer collateral-CA1 (Sch-CA1), temporoammonic-CA1 (TA-CA1) and perforant pathway-dentate gyrus (PP-DG) synapses in transverse slices from the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus in adult male rats. After repeated morphine exposure, the expression of opioid receptors and the α1 and α5 GABA A subunits were also examined. We found that repeated morphine exposure blunt the difference between the DH and the VH in their basal levels of synaptic transmission at Sch-CA1 synapses that were seen in the control groups. Significant paired-pulse facilitation of excitatory synaptic transmission was observed at Sch-CA1 synapses in slices taken from all three hippocampal segments as well as at PP-DG synapses in slices taken from the VH segment in the morphine-treated groups as compared to the control groups. Interestingly, significant paired-pulse inhibition of excitatory synaptic transmission was observed at TA-CA1 synapses in the DH slices from the morphine-treated group as compared to the control group. While primedburst stimulation (a protocol reflecting normal neuronal firing) induced a robust LTP in hippocampal subfields in all control groups, resulting in a decaying LTP at TA-CA1 synapses in the VH slices and at PP-DG synapses in both the IH and VH slices taken from the morphine-treated rats. In the DH of morphine-treated rats, we found increased levels of the mRNAs encoding the α1 and α5 GABA A subunits as compared to the control group. Taken together, these findings suggest the potential mechanisms through which repeated morphine exposure causes differential changes in circuit excitability and synaptic plasticity in the dentate gyrus and CA1 regions along the hippocampal long axis.

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Section: Discussionmentioning

confidence: 99%

Section: Rme Increases the Expression Of Gaba A Receptor α1 And α5 Su...mentioning

confidence: 99%

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

et al. 2022

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“…The α1 subunit constitute the dominant interface where benzodiazepines bind and it is necessary for a rapid formation of active synaptic contacts and the synaptogenesis effect. This subunit has been shown to associate with learning deficit in epilepsy, stress resilience and mediates plasticity in context-dependent learning [ 9 ]. The α2 subunit is located on the axon initial segment (AIS) and is involved in the reduction of postsynaptic inhibitory output and IPSC (inhibitory postsynaptic current) amplitude, morphine express and acquisition-expression of morphine reward at the dorsal hippocampus [ 10 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits

et al. 2021

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Background ɣ-aminobutyric acid (GABA) facilitator valproic acid may be able to curb memory disruption induced by morphine exposure. Objective The effects of the GABA facilitator valproic acid on the behavioral tolerance induced by morphine were investigated. Then hippocampal-dependent tasks named spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Finally, the changes in the expression of hippocampal GABA-A receptors underlying morphine tolerance were also examined. Methods Rats were treated with daily morphine injections, with or without distinct contextual pairing. To examine the effect of valproic acid on morphine tolerance expression, valproic acid was pretreated an hour before morphine. Spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Afterwards the changes in the expression of hippocampal GABAα receptors using the quantitative real-time PCR and western blot techniques to detect GABArα subunits mRNAs and protein level were studied. Results Our results showed that both learned and non-associative morphine tolerance influence short-term memory and the subjacent expression of GABArα mRNAs and protein level. Despite its attenuating effects on the development and expression of both learned and non-associative morphine tolerance, only associative morphine tolerance-induced memory dysfunction was ameliorated by valproic acid pretreatment. We also found that the expression of GABArα1, α2, α5 subunits mRNAs and GABAα protein level were affected heavier in associative morphine tolerant rats. Conclusion Our data supports the hypothesis that unconditioned and learned morphine tolerance influences short-term memory and the expression of GABArα 1, α2, α5 mRNAs and GABArα protein level differently, and adds to our understanding of the behavioral and molecular aspects of the learned tolerance to morphine effects.

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“…Flurothyl is a GABAA antagonist with epileptogenic ability [ 23 ]. Acute generalized tonic-clonic seizure mouse model can be established by flurothyl inhalation [ 24 - 26 ], which manifests as convulsions and tonic extension of the limbs [ 27 , 28 ]. The rats with recurrent seizures induced by flurothyl usually present reflex delay, poor adaptation to new environments, and poor memory and learning abilities [ 27 ].…”

Section: Generalized Tonic-clonic Seizure Modelsmentioning

confidence: 99%

“…Acute generalized tonic-clonic seizure mouse model can be established by flurothyl inhalation [ 24 - 26 ], which manifests as convulsions and tonic extension of the limbs [ 27 , 28 ]. The rats with recurrent seizures induced by flurothyl usually present reflex delay, poor adaptation to new environments, and poor memory and learning abilities [ 27 ]. A previous study revealed that the classical pathological changes in flurothyl-kindling mice with Angelman syndrome were perineuronal net deposition in the dentate gyrus without obvious mossy fiber sprouting or neuronal loss [ 29 ].…”

Section: Generalized Tonic-clonic Seizure Modelsmentioning

confidence: 99%

Animal Models of Epilepsy: A Phenotype-oriented Review

Wang¹,

Wei²,

Feng³

et al. 2022

Aging and disease

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Epilepsy is a serious neurological disorder characterized by abnormal, recurrent, and synchronous discharges in the brain. Long-term recurrent seizure attacks can cause serious damage to brain function, which is usually observed in patients with temporal lobe epilepsy. Controlling seizure attacks is vital for the treatment and prognosis of epilepsy. Animal models, such as the kindling model, which was the most widely used model in the past, allow the understanding of the potential epileptogenic mechanisms and selection of antiepileptic drugs. In recent years, various animal models of epilepsy have been established to mimic different seizure types, without clear merits and demerits. Accordingly, this review provides a summary of the views mentioned above, aiming to provide a reference for animal model selection.

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Recurrent seizures cause immature brain injury and changes in GABA a receptor α1 and γ2 subunits

Cited by 6 publications

References 45 publications

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

A distinct impact of repeated morphine exposure on synaptic plasticity at Schaffer collateral‐CA1, temporoammonic‐CA1, and perforant pathway‐dentate gyrus synapses along the longitudinal axis of the hippocampus

Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits

Animal Models of Epilepsy: A Phenotype-oriented Review

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