The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases

Wu, Qinglin; Gao, Yan; Li, Juntong; Ma, Wen-Yu; Chen, Nai‐Hong

doi:10.1007/s10571-021-01141-z

Cited by 20 publications

(10 citation statements)

References 109 publications

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“…Therefore, we chose 0-Mg 2+ -induced primary neurons as our in vitro model. [58][59][60] In our study, PcTX1 was found to rescue 0-Mg 2+ -induced neuron death, rebalance the Ca 2+ homeostasis, and alleviate ROS production induced by 0-Mg 2+ . However, the detailed mechanism of PcTX1 exerting neuroprotective effects remains unclear.…”

Section: Discussionsupporting

confidence: 50%

Inhibiting acid‐sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis

Shi,

Liu,

Wang

et al. 2024

CNS Neurosci Ther

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BackgroundEpilepsy is a chronic neurological disease characterized by repeated and unprovoked epileptic seizures. Developing disease‐modifying therapies (DMTs) has become important in epilepsy studies. Notably, focusing on iron metabolism and ferroptosis might be a strategy of DMTs for epilepsy. Blocking the acid‐sensing ion channel 1a (ASIC1a) has been reported to protect the brain from ischemic injury by reducing the toxicity of [Ca2+]i. However, whether inhibiting ASIC1a could exert neuroprotective effects and become a novel target for DMTs, such as rescuing the ferroptosis following epilepsy, remains unknown.MethodsIn our study, we explored the changes in ferroptosis‐related indices, including glutathione peroxidase (GPx) enzyme activity and levels of glutathione (GSH), iron accumulation, lipid degradation products‐malonaldehyde (MDA) and 4‐hydroxynonenal (4‐HNE) by collecting peripheral blood samples from adult patients with epilepsy. Meanwhile, we observed alterations in ASIC1a protein expression and mitochondrial microstructure in the epileptogenic foci of patients with drug‐resistant epilepsy. Next, we accessed the expression and function changes of ASIC1a and measured the ferroptosis‐related indices in the in vitro 0‐Mg2+ model of epilepsy with primary cultured neurons. Subsequently, we examined whether blocking ASIC1a could play a neuroprotective role by inhibiting ferroptosis in epileptic neurons.ResultsOur study first reported significant changes in ferroptosis‐related indices, including reduced GPx enzyme activity, decreased levels of GSH, iron accumulation, elevated MDA and 4‐HNE, and representative mitochondrial crinkling in adult patients with epilepsy, especially in epileptogenic foci. Furthermore, we found that inhibiting ASIC1a could produce an inhibitory effect similar to ferroptosis inhibitor Fer‐1, alleviate oxidative stress response, and decrease [Ca2+]i overload by inhibiting the overexpressed ASIC1a in the in vitro epilepsy model induced by 0‐Mg2+.ConclusionInhibiting ASIC1a has potent neuroprotective effects via alleviating [Ca2+]i overload and regulating ferroptosis on the models of epilepsy and may act as a promising intervention in DMTs.

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Section: Discussionsupporting

confidence: 50%

Inhibiting acid‐sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis

Shi,

Liu,

Wang

et al. 2024

CNS Neurosci Ther

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“… 56 Studies have shown that AMPA receptors are expressed throughout the brain, and their normal activation is essential for modulation of synaptic plasticity (such as long-term potential enhancement (LTP) and long-term depression (LTD)). 57 LTP and LTD can occur on the hypothalamic synapses, which are important for attacking. 58 LTP is part of the causal mechanism and increases aggressiveness through repeated successful attacks.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with the non-aggressive control group, the levels of AMPA receptors in the isolation-induced aggressive mice were significantly higher in the amygdala and prefrontal cortex . Studies have shown that AMPA receptors are expressed throughout the brain, and their normal activation is essential for modulation of synaptic plasticity (such as long-term potential enhancement (LTP) and long-term depression (LTD)) . LTP and LTD can occur on the hypothalamic synapses, which are important for attacking .…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Proteomic Analysis in Male Mice Following Aggressive Behavior Induced by Long-Term Administration of Perampanel

Yang

Hai

et al. 2022

ACS Omega

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Antiepileptic drugs have been shown to be associated with inducing or exacerbating adverse psychotropic reaction, including aggressive behavior. Perampanel, the first pharmacological compound approved by the FDA in 2012, is an effective antiepileptic drug for intractable epilepsy but induces severe aggression. So far, the underlying molecular mechanisms of aggression induced by perampanel remain incompletely understood. In the present study, a model of aggressive behavior based on the clinical use of perampanel was established and resident–intruder test and open field test were performed. Changes in hippocampal protein profiles were detected by tandem mass tag (TMT) proteomics. The behavioral results indicated that long-term use of perampanel increased the aggressive behavior of C57BL/6J mice. Proteomic analysis revealed that 93 proteins were significantly altered in the hippocampus of the perampanel-treated group (corrected p < 0.05), which were divided into multiple functional groups, mainly related to synaptic function, synaptogenesis, postsynaptic density protein, neurite outgrowth, AMPA-type glutamate receptor immobilization, and others. Bioinformatic analysis showed that differentially expressed proteins were involved in synaptic plasticity and the Ras signaling pathway. Furthermore, validation results by western blot demonstrated that glutamate receptor 1 (GluA1) and phosphorylation of mitogen-activated protein kinase (ERK1/2) were notably up-regulated, and synaptophysin ( Syn ) and postsynaptic density 95 (PSD95) were down-regulated in perampanel-treated mice. Therefore, our results provide valuable insight into the molecular mechanisms of aggressive behavior induced by perampanel, as well as potential options for safety treatment of perampanel in the future.

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“…The amino‐terminal domain (ATD) of GluA1 is essential for maintaining LTP and is involved in regulating neuronal development, LTP, and synaptic transmission (Jiang, Wei, et al., 2021). GluA2 is the only subtype among the four that possesses RNA editing capability (Wu et al., 2021). GluA2 is primarily found in the central nervous system.…”

Section: Role Of Synaptic Plasticity‐related Proteins In Maintaining ...mentioning

confidence: 99%

Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship

Zhu,

Hui,

Zhang

et al. 2024

J of Neuroscience Research

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Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth‐associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.

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The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases

Cited by 20 publications

References 109 publications

Inhibiting acid‐sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis

Inhibiting acid‐sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis

Hippocampal Proteomic Analysis in Male Mice Following Aggressive Behavior Induced by Long-Term Administration of Perampanel

Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship

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