2026-10-13T19:10:21Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33980059 2026-09-24T05:59:23Z category_4 category_14 category_15 category_16 category_122 portal_87 item_type_3 month_year_09_2026

Perampanel improves cognitive function in epilepsy by targeting AMPA receptor subunit GluR2-mediated endoplasmic reticulum stress and synaptic plasticity Xiaoqin Wang (12030) Bin Lei (172773) Yao Zhou (1521676) Foyang Fan (25102381) Liang Huang (114017) Shuzhen Luo (4792995) Liping Zhang (177396) Youfeng Zhou (25102384) Biochemistry Molecular Biology Neuroscience Physiology Mental Health Epilepsy refractory epilepsy perampanel AMPA receptor subunit GluR2 endoplasmic reticulum stress synaptic plasticity <p>This study aimed to explore the action mechanism of Perampanel (PER) in epilepsy treatment, particularly the associations with endoplasmic reticulum stress (ERS).</p> <p>Epilepsy mice model was induced by injecting kainic acid (KA) into hippocampus of mice, and KA-stimulated hippocampal neurons were used as <i>in vitro</i> cell model. Cognitive function of mice was evaluated by Novel Object Recognition and Morris Water maze tests. Hematoxylin-eosin and Nissl staining were conducted to observe neuron damage. Synaptic plasticity was evaluated by Golgi staining, immunofluorescence staining of microtubule-associated protein (MAP2) and synaptic function proteins expression. The 4-phenylbutyric acid (4-PBA) was used to inhibit ERS in cells.</p> <p>PER treatment markedly ameliorated epileptic seizure behaviors, improved the spatial learning and memory functions, and hippocampal neuron injury of KA-induced epilepsy mice model. Moreover, KA-induced epilepsy mice showed reduced GluR2 expression, decreased dendritic spine density and expression of synaptic function proteins (SYP and PSD95) as well as elevated ERS-related proteins (GRP78, ATF4, CHOP, IRE1α and ATF6), while PER treatment could reverse such changes. Meanwhile, PER treatment could alleviate KA-induced neurotoxicity and synaptic plasticity deficits in hippocampal neurons. In terms of mechanism, GluR2 silencing reversed the protective effects of PER in KA-stimulated hippocampal neurons, and further inhibiting ERS using 4-PBA could offset the effects of GluR2 silencing.</p> <p>GluR2-mediated ERS may involve the improved effects of Perampanel in cognitive function of epilepsy patients by promoting synaptic plasticity.</p> <p></p><p>Perampanel effectively alleviates epileptic seizure behaviors and improves cognitive function</p><p>Perampanel upregulates the expression of AMPA receptor subunit GluR2, thus reducing Ca²⁺ influx</p><p>GluR2 silencing reverses the therapeutic effects of Perampanel in epilepsy</p><p></p> <p>Perampanel effectively alleviates epileptic seizure behaviors and improves cognitive function</p> <p>Perampanel upregulates the expression of AMPA receptor subunit GluR2, thus reducing Ca²⁺ influx</p> <p>GluR2 silencing reverses the therapeutic effects of Perampanel in epilepsy</p> 2026-09-24T05:59:23Z Dataset Dataset 10.6084/m9.figshare.33980059.v1 https://figshare.com/articles/dataset/Perampanel_improves_cognitive_function_in_epilepsy_by_targeting_AMPA_receptor_subunit_GluR2-mediated_endoplasmic_reticulum_stress_and_synaptic_plasticity/33980059 CC BY 4.0