Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Alternating hemiplegia of childhood misdiagnosed as hysteria: a case report

Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis movements,anomalous ocular motions,and a gradual deterioration in cognitive function.The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentation Here,we report a 16-year-old girl with recurrent hemiplegia since her infancy.This patient has experienced paroxysmal limb weakness and aphasia for over 15 years,and has kept seeking medical attention but without receiving effective treatment.A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital.Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C(p.Leu757Pro)mutation in her ATP1A3 gene.Notably,her clinical manifestations,including pathological emotional responses and autonomic dysfunction,differed from the established profile associated with the same ATP1A3 mutation,which typically present with intellectual disability,a rostrocaudal symptom gradient,choreoathetosis,and dysarthria.The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.Conclusions This case enhances our understanding of the intricate clinical manifestations of AHC,which require careful differentiation from various diseases such as epilepsy,hysteria,and paroxysmal dyskinesias.In the diagnosis of patients presenting with suspected symptoms,adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments.Additionally,when AHC is suspected in a patient,genetic testing should be considered as part of the diagnostic approach.

NO transport characteristics in microcirculation and its implications in the assessment of microvascular dysfunction in type 2 diabetes mellitus

Diabetes mellitus is a metabolic disorder syndrome caused by various pathogenic factors leading to imbalance of active substance secretion and endothelial dysfunction,causing macro and micro vascular complications.As the most important signal transduction molecule released by endothelium,NO participates in various physiological processes of microcirculation and plays an important role in vascular relaxation regulation.Extensive studies focus on the investigation of the analysis of NO transport in microvessels,RBC motion and its influence on NO transport since they are of extremely importance for understanding the mechanisms of vessel autoregulation and microcirculation lesion.NO transport characteristics are closely associated with hemorheology,hemodynamics and microvascular structure.Nevertheless,up to date,there are limited reports on NO transport characteristics in diabetic mellitus.The purpose of this review is to summarize the current advances in the investigation of NO transport characteristics from cellular to vascular level,which can provide effective ideas for the early diagnosis of vascular complications in diabetes.