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Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

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Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi Federica Cherchi Alasdair J.Gibb Department of Neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly Department of Neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue ***,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy *** neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic *** indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 *** recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose *** demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor *** present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

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medium spiny neurons of the anterior dorsomedial striatum(aDMS) mediate cognitive flexibility in a cell-type dependent manner

Medium spiny neurons of the anterior dorsomedial striatum(aD...

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第六届心理健康学术年会

作者： Xingyue Wang Yanhua Qiao Nan Sui Jing Liang Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences

The deficits in cognitive flexibility are commonly observed in many mental disorders, including Parkinson’s disease(PD), schizophrenia, and drug addiction. Although striatum has been implicated in regulating flexible behaviors, the exact subregion which associate in these behaviors is still unclear in this heterogeneous brain *** the striatum subareas, the anterior part of the dorsomedial striatum(aDMS) is reported to play particular role in the pathology of these disorders with cognitive inflexibility. The aDMS mainly consists of two types of neurons(D1R-and D2R-MSNs). However, the exact role of these neurons and their projections in cognitive flexibility are still *** clarify the specific function of aDMS projections in cognitive flexibility, we used optogenetic approach to clarify the roles of D1R direct and D2R indirect pathways in the aDMS in mediating cognitive flexibility with a *** activities in the medialdorsal thalamus(MD),a downstream region of the striatum, were identified in functional pattern by using immonochemicohistory following light-stimulation-modulated *** found seversal observations. Activation of D1R-MSNs in aDMS impaired reversal learning and behavioral extinction, while activation of D2R-MSNs in this brain area facilitated the strategy reverse and extinction. Accordingly, the neuronal activity in MD thalamus,was down-regulated or up-regulated,with disruption or facilitation of reversal performance.

关键词： Anterior dorsomedial striatum behavioral flexibility optogenetics medium spiny neurons dopamine receptors

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Single Exposure to Cocaine Impairs Reinforcement Learning by Potentiating the Activity of neurons in the Direct Striatal Pathway in Mice

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Neuroscience Bulletin 2021年第8期37卷 1119-1134页

作者： Zhijun Diao Yuanyuan Di Meilin Wu Chenyang Zhai Mengsi Kang Yongfeng Li Yingxun Liu Chunling Wei Qiaohua Zheng Jing Han Zhiqiang Liu Yingfang Tian Wei Ren Key Laboratory of Modern Teaching Technology Ministry of EducationShaanxi Normal UniversityXi’an710062China College of Life Sciences Shaanxi Normal UniversityXi’an710119China

Plasticity in the glutamatergic synapses on striatal medium spiny neurons(MSNs)is not only essential for behavioral adaptation but also extremely vulnerable to drugs of *** on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce *** the present work,we found that the negative reinforcement learning,escaping mild foot-shocks by correct nose-poking,was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in *** a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1(D1)receptor(D1-MSNs).However,24 h after the cocaine exposure,the potentiation required for reinforcement learning was *** manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice,but inhibition of these neurons reversed the reinforcement learning impairment induced by *** results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.

关键词： Cocaine Reinforcement learning Striatum medium spiny neurons Long-term potentiation

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Therapeutic advances in neural regeneration for Huntington’s disease

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Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito Annamaria Cimini Michele d’Angelo Department of Life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic medium spiny neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to o

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

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Parkinson’s disease and translational research

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Translational Neurodegeneration 2020年第4期9卷 547-557页

作者： Elisabeth Dinter Theodora Saridaki Leonie Diederichs Heinz Reichmann Bjorn H.Falkenburger Department of Neurology Technische Universitat DresdenDresdenGermany Deutsches Zentrum fur Neurodegenerative Erkrankungen DresdenGermany Department of Neurology RWTH University AachenAachenGermany

Parkinson's disease(PD)is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity,and when these symptoms respond to dopaminergic *** in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous *** this review we discuss current concepts of two major alterations found during the course of the disease:cytoplasmic aggregates of the protein a-synuclein and the degeneration of dopaminergic *** provide an overview of new approaches in this field based on current concepts and latest *** many areas,translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.

关键词： α-Synuclein Pre-formed fibrils Protein aggregates Aggresome Dopamine deficiency medium spiny neurons Autophagy

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Histamine postsynaptically excites dopamine D1 and D2 receptor-expressing striatal neurons via H1 and H2 receptors in rats

Histamine postsynaptically excites dopamine D1 and D2 recept...

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中国神经科学学会第十二届全国学术会议

作者： Qian-Xing ZHUANG Han-Ting XU Xu-Juan LU Bin LI Wing-Ho YUNG Jian-Jun WANG Jing-Ning ZHU State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology School of Life Sciences Nanjing University Nanjing Institute of Visual Arts School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong

The central histaminergic nervous system, originating from the tuberomammillary nucleus（TMN） of the hypothalamus, widely innervates almost the whole brain, including the basal ganglia. Here, by using anterograde tracing, immunostaining and patch clamp recording techniques, we investigate the histaminergic afferents in the striatum, the major input structure of the basal ganglia, as well as the effect of histamine on the striatal GABAergic medium spiny projection neurons（MSNs）. We report a direct histaminergic projection from the hypothalamic TMN to the striatum. Furthermore, histamine exerts a postsynaptic excitatory effect on both dopamine D1 and D2 receptor-expressing MSNs. The concentration-response curves and the EC50 values for histamine on two types of MSNs are similar. In addition, both histamine H1 and H2 receptors are co-localized on dopamine D1 and D2 receptor-expressing MSNs, and comediate the histamine-induced excitation on two types of neurons. These results suggest that the histaminergic afferent inputs in the striatum may modulate both dopamine D1 and D2 receptor-expressing MSNs by activation of postsynaptic histamine H1 and H2 receptors and thus function as an important extrastriatal modulator for the direct and indirect pathway of the basal ganglia.

关键词： Histamine Striatum medium spiny neurons Histamine receptors Dopamine receptors

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