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.Meta...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.展开更多
从大鼠的尾壳核组织中提取总 RNA,以 RT-PCR方法扩增出大鼠 m Glu R5 长度约 43 5 bp的 c DNA片段。将这一片段克隆到 PGEM-T载体中进行序列分析 ,结果证实所克隆的 c DNA是编码正确的大鼠 m Glu R5 的一段基因序列。克隆的这段大鼠m Gl...从大鼠的尾壳核组织中提取总 RNA,以 RT-PCR方法扩增出大鼠 m Glu R5 长度约 43 5 bp的 c DNA片段。将这一片段克隆到 PGEM-T载体中进行序列分析 ,结果证实所克隆的 c DNA是编码正确的大鼠 m Glu R5 的一段基因序列。克隆的这段大鼠m Glu R5 特异性基因片段可用于制作探针 ,利用原位杂交技术检测其 m RNA在正常或异常状况下的表达 ;也可制作反意 c DNA或反意 m RNA以研究 m Glu R5 在生理或病理状态下的作用 ;还可进行反意 c DNA或反意 m RNA基因治疗。总而言之 ,克隆的这段基因 ,对研究 m Glu R5 在生理及病理条件下的功能变化 。展开更多
Understanding the cellular mechanisms of drug addiction remains a key task in current brain research.While neuron-based mechanisms have been extensively explored over the past three decades,recent evidence indicates a...Understanding the cellular mechanisms of drug addiction remains a key task in current brain research.While neuron-based mechanisms have been extensively explored over the past three decades,recent evidence indicates a critical involvement of astrocytes,the main type of non-neuronal cells in the brain.In response to extracellular stimuli,astrocytes modulate the activity of neurons,synaptic transmission,and neural network properties,collectively influencing brain function.G protein-coupled receptors(GPCRs)expressed on astrocyte surfaces respond to neuron-and environment-derived ligands by activating or inhibiting astrocytic signaling,which in turn regulates adjacent neurons and their circuitry.In this review,we focus on the dopamine D1 receptors(D1R)and metabotropic glutamate receptor 5(mGLUR5 or GRM5)—two GPCRs that have been critically implicated in the acquisition and maintenance of addiction-related behaviors.Positioned as an introductory-level review,this article briefly discusses astrocyte biology,outlines earlier discoveries about the role of astrocytes in substance-use disorders(SUDs),and provides detailed discussion about astrocytic D1Rs and mGLUR5s in regulating synapse and network functions in the nucleus accumbens(NAc)—a brain region that mediates addictionrelated emotional and motivational responses.This review serves as a stepping stone for readers of Engineering to explore links between astrocytic GPCRs and drug addiction and other psychiatric disorders.展开更多
基金supported by the National Natural Science Foundation of China(No.81973988)Henan Key Laboratory of Neurorestoratology Foundation(No.HNSJXF-2021-014)the Graduate Innovation Program of Xinxiang Medical University(No.202122Z)。
基金supported by the Natural Science Foundation of Hunan Province,No.2021JJ30389(to JG)the Key Research and Development Program of Hunan Province of China,Nos.2022SK2042(to LL)and 2020SK2122(to ET)。
文摘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.
文摘从大鼠的尾壳核组织中提取总 RNA,以 RT-PCR方法扩增出大鼠 m Glu R5 长度约 43 5 bp的 c DNA片段。将这一片段克隆到 PGEM-T载体中进行序列分析 ,结果证实所克隆的 c DNA是编码正确的大鼠 m Glu R5 的一段基因序列。克隆的这段大鼠m Glu R5 特异性基因片段可用于制作探针 ,利用原位杂交技术检测其 m RNA在正常或异常状况下的表达 ;也可制作反意 c DNA或反意 m RNA以研究 m Glu R5 在生理或病理状态下的作用 ;还可进行反意 c DNA或反意 m RNA基因治疗。总而言之 ,克隆的这段基因 ,对研究 m Glu R5 在生理及病理条件下的功能变化 。
基金partially supported by the National Institutes of Health(NIH)grants DA056213(to Alexander K.Zinsmaier),DA053388(to Eric J.Nestler),DA023206(to Yan Dong),DA060868(to Yan Dong),and DA040620(to Eric J.Nestler and Yan Dong)。
文摘Understanding the cellular mechanisms of drug addiction remains a key task in current brain research.While neuron-based mechanisms have been extensively explored over the past three decades,recent evidence indicates a critical involvement of astrocytes,the main type of non-neuronal cells in the brain.In response to extracellular stimuli,astrocytes modulate the activity of neurons,synaptic transmission,and neural network properties,collectively influencing brain function.G protein-coupled receptors(GPCRs)expressed on astrocyte surfaces respond to neuron-and environment-derived ligands by activating or inhibiting astrocytic signaling,which in turn regulates adjacent neurons and their circuitry.In this review,we focus on the dopamine D1 receptors(D1R)and metabotropic glutamate receptor 5(mGLUR5 or GRM5)—two GPCRs that have been critically implicated in the acquisition and maintenance of addiction-related behaviors.Positioned as an introductory-level review,this article briefly discusses astrocyte biology,outlines earlier discoveries about the role of astrocytes in substance-use disorders(SUDs),and provides detailed discussion about astrocytic D1Rs and mGLUR5s in regulating synapse and network functions in the nucleus accumbens(NAc)—a brain region that mediates addictionrelated emotional and motivational responses.This review serves as a stepping stone for readers of Engineering to explore links between astrocytic GPCRs and drug addiction and other psychiatric disorders.
