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Inhibition of Nav1.8 channels reduces pain-related spontaneous activity in DRG after spinal cord injury

Inhibition of Nav1.8 channels reduces pain-related spontaneo...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Junhui Du Susan M.Carlton Neurosci & Cell Biol Univ.Texas Medical Branch

The severe, chronic pain that often follows spinal cord injury(SCI) is thought to depend upon alterations in spinal and supraspinal neurons. Our findings shows that an increased spontaneous activity(SA) in DRG is generated after contusion, and such increased SA lasts from 30 min to 2 months. It might contribute to central sensitization and neuropathic pain after SCI, just as nociceptor SA contributes to pain after peripheral injury and inflammation. Nav1.8 is a tetrodotoxin(TTX)-resistant voltage-gated sodium ion channel. It is expressed specifically in the dorsal root ganglion(DRG) small-diameter sensory neurons and is involved in the pain. The modulation of Nav1.8 in sensory neurons of the DRG may be the key factor in therapeutic targets for the development of new analgesics and to treat chronic pain. To test this hypothesis we are examining SA in possible nociceptors in vivo. A-803467, potently blocks NaV1.8 channels, was applied on the DRG. And the SCI induced SA was significantly block after A-803467 application. The results imply that Nav1.8 is an important target for exploring the mechanisms of SCI induced SA, and may provide a new area to treat chronic pain.

关键词： spinal cord injury,DRG,Nav1.8

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The Mechanical Effect of Surgical Trauma on Alcohol Administration

The Mechanical Effect of Surgical Trauma on Alcohol Administ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jie Liu Xiaojian Li Hui Zhao Department of Integrative Medicine School of Basic Medical SciencesFudan University

Alcohol abuse and addiction are huge obsessions to people invoking severe social problem. Previous Studies show that trauma can enhance alcohol administration following neuroinflammation in TBI. Clinical surgical trauma can also cause neuroinflammation whose degree is constantly changing. Evidences uncovered that people post-surgery have greater preference to alcohol than common people producing enormous harm to patient and his family. So researching mechanism of surgical trauma to alcohol administration is urgent. In our work, we constructed surgical trauma model with male SD rats, then exposure to alcohol(10%, v/v) and water in 2-bottle choice drinking paradigm from post-trauma 1, 3, 7 day. And it conducted 4 hours and 24 hours each day for 19 days. Results indicate that 4-hour alcohol intake and preference show a significant increase in T3 compared with control and T1 in 24-hour testing. So surgical trauma can influence alcohol intake and preference in certain post-trauma stage, and the duration of taking alcohol can influence the response. In general, our research demonstrates the relationship between surgical trauma and alcohol administration and directs us to solve the problem of alcohol abuse and addiction.

关键词： Alcohol abuse and addiction neuroinflammation clinical surgical trauma

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Histone demethylase PHF8 deficiency causes cognitive impairments through the mTOR pathway

Histone demethylase PHF8 deficiency causes cognitive impairm...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Weidong LI Shanghai Jiao Tong University

X-linked mental retardation(XLMR) is a heterogeneous condition affecting approximately 0.2% men, and there is currently no drug treatment. PHF8(plant homeodomain finger protein 8) is histone demethylase for H3K9me2 and H4K20me1, and mutations of the gene are found in X-link mental retardation patients. Here we show that PHF8 knockout impairs cognitive functions, including spatial learning and memory and contextual fear memory in mice, as well as the reduced long term potentiation in the hippocampus. m RNA profiling and chromatin immunoprecipitation indicate that PHF8 directly regulates RSK1, a ribosomal protein S6 kinase involved in the mT OR signaling. Using a pharmacological approach, we further demonstrate that a brief treatment with the mT OR inhibitor rapamycin can ameliorate the deficits of learning and memory, and reverse the long term potentiation in knockout mice. Thus, our results reveal that histone demethylase PHF8 deficiency causes cognitive impairment at least through the RSK-mT OR pathway, and targeting the mT OR pathway may have potential therapeutic effects on PHF8 associated X-link mental retardation.

关键词： PHF Histone demethylase PHF8 deficiency causes cognitive impairments through the mTOR pathway

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The fine structure of the compound eye and optic lobe of the two-spotted cricket Gryllus bimaculatus

The fine structure of the compound eye and optic lobe of the...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jie Na Xue Leng Yu-Peng Na College of Chemistry & Life Sciences Shenyang Normal University Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications Ministry of Education of China

【Objectives】 To investigate the important structural pathway of insect visual signal processing by observing and describing the histological structural features of the compound eyes and optic lobes of the cricket, Orthoptera Gryllidae. 【Methods】The histological structure of the compound eye and optic lobe of 30 crickets was observed and analyzed using scanning electron microscopy and histological biopsy techniques. 【Results】 The compound eye was comprised of about 3,400 small hexagonal eyes. In the gaps between the small eyes, there are mechanoreceptors, which are sensory hair and bell-shaped receptors. Each small eye is comprised of a cornea, crystalline cone, rhabdome, 6 retinal cells and basement membrane, etc. The optic lobe has two fan-shaped structures and is comprised of three major networks of nerve fibers, the ganglion layer, outer medulla and inner medulla.【Conclusion】 There are a few sensory hairs and bell-shaped receptors on the surface of the compound eyes of crickets. Each small eye is comprised of a cornea, crystalline cone, rhabdome, 6 retinal cells, basement membrane, etc. and the arrangement of small eyes is juxtaposed. The optic lobe is comprised of three major networks of nerve fibers.

关键词： Gryllus bimaculatus,compound eyes,optic lobe,histological structure

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Acrylamide induces locomotor defects and degeneration of dopamine neurons in Caenorhabditis elegans

Acrylamide induces locomotor defects and degeneration of dop...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jia Li Dan Li Yong-Sheng Yang Tian-Tian Xu Ping Li De-Fu He Lab of Toxicology School of Ecological and Environmental SciencesEast China Normal University Shanghai Key Lab for Urban Ecological Processes and Eco-Restoration

Acrylamide can form in foods during cooking process and cause multiple adverse effects. However, the neurotoxicity and mechanisms of acrylamide have not been fully elucidated. In Caenorhabditis elegans, we showed that 48 h exposure to 10-625 mg/L acrylamide resulted in significant declines in locomotor frequency of body bending, head thrashing, and pharynx pumping. In addition, acrylamide exposure reduced crawling speeds and changed angles of body bending. It indicates that acrylamide induce locomotor defects, along with Parkinsonian-like movement impairment including bradykinesia and hypokinesia. Acrylamide also affected chemotaxis plasticity and reduced learning ability. Using transgenic nematodes, we found that acrylamide induced down-expression of Pdat-1 and led to the degeneration of dopaminergic neurons. Moreover, the enhanced expression of unc-54, encoding a subunit of α-synuclein was found. It illustrates that acrylamide is efficient in inducing crucial Parkinsonian pathology including dopaminergic damage and α-synuclein aggregation. These findings suggest the acrylamide-induced locomotor defects and neurotoxicity are associated with Parkinson's disease.

关键词： Acrylamide Caenorhabditis elegans Locomotor behaviors dopaminergic neurons α-synuclein Parkinson's disease

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Genetic association and autoimmunological mechanisms of narcolepsy

Genetic association and autoimmunological mechanisms of narc...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Fang Han Department of Pulmonary Medicine Beijing University People's Hospital

Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and disturbed nocturnal sleep. Narcolepsy is caused by the loss of hypocretin(orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4(also called OX40L), Cathepsin H(CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections in 2010 following the 2009 H1N1 pandemic(p H1N1) in China and following AS03-adjuvanted p H1N1 influenza vaccination in Northern Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons, and are likely a combination of genetic and environmental factors, such as upper airway infections.

关键词： Narcolepsy,H1N1,Gene,Hypocretin

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Octopamine mediates starvation-induced hyperactivity in adult Drosophila

Octopamine mediates starvation-induced hyperactivity in adul...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Zhe Yang Yue Yu Vivian Zhang Yinjun Tian Wei Qi Liming Wang Life Sciences Institute Zhejiang University Department of Molecular and Cell Biology University of California College of Life Sciences Sichuan University

Starved animals often exhibit elevated locomotion, which has been speculated to partly resemble foraging behavior and facilitate food acquisition and energy intake. Despite its importance, the neural mechanism underlying this behavior remains unknown in any species. In this study we confirmed and extended previous findings that starvation induced locomotor activity in adult fruit flies Drosophila melanogaster. We also showed that starvation-induced hyperactivity was directed toward the localization and acquisition of food sources, because it could be suppressed upon the detection of food cues via both central nutrient-sensing and peripheral sweet-sensing mechanisms, via induction of food ingestion. We further found that octopamine, the insect counterpart of vertebrate norepinephrine, as well as the neurons expressing octopamine, were both necessary and sufficient for starvation-induced hyperactivity. Octopamine was not required for starvation-induced changes in feeding behaviors, suggesting independent regulations of energy intake behaviors upon starvation. Taken together, our results establish a quantitative behavioral paradigm to investigate the regulation of energy homeostasis by the CNS and identify a conserved neural substrate that links organismal metabolic state to a specific behavioral output.

关键词： Drosophila starvation foraging octopamine

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Delineation of the central melanocortin circuitry controlling the kidneys by a virally mediated transneuronal tracer

Delineation of the central melanocortin circuitry controllin...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Tao-Tao Liu Zhi-Gang He Da-Wei Ye Xue-Bi Tian Hong-Bing Xiang Department of Anesthesiology and Pain Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Cancer center Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

To examine if CNS neurons involved in the regulation of the kidneys possess melanocortin-4 receptor(MC4R) and/or tryptophan hydroxylase(TPH). A modified retrograde transsynaptic tracer pseudorabies virus(PRV)-614 was injected into the kidney in adult male MC4R-GFP mouse. 3-7d after injection, spinal cord and brain were removed and sectioned, and PRV-614-positive cells was identified using double or triple immunocytochemical labeling against PRV-614, MC4 R, or TPH. The majority of PRV-614-positive neurons which expressed immunoreactivity for GFP were located in the thoracic spinal ipsilateral intermediolateral cell column(IML), paraventricular nucleus(PVN) of hypothalamus, and raphe pallidus(RPa), nucleus raphe magnus(NRM) and ventromedial medulla(VMM) of the brainstem. Triple-labeled MC4R/PRV-614/TPH neurons were concentrated in the PVN, RPa, NRM and VMM. These data strongly suggest that MC4 R and TPH may be implicated in the central control of renal function.

关键词： Central melanocortin circuitry Kidney Pseudorabies virus Neurochemical phenotype Melanocortin-4 receptor Tryptophan hydroxylase

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Itch receptors and coding

Itch receptors and coding

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Xinzhong Dong Departments of Neuroscience and Neurosurgery Johns Hopkins UniversitySchool of Medicine Howard Hughes Medical Institute Johns Hopkins UniversitySchool of Medicine

Despite of the clinical importance, cell surface receptors mediating non-histaminergic itch are largely unknown. We identified a large family of G protein-coupled receptors in mice called Mrgprs. Many of these receptors are exclusively expressed in distinct subsets of small-diameter dorsal root ganglion(DRG) neurons. We found that Mrgpr A3 functions as a receptor for chloroquine(an anti-malaria drug) and is required for chloroquine-induced itch. Besides chloroquine, Mrgprsalso respond to several itch-inducing compounds such as BAM8-22, SLIGRL, and beta-alanine suggesting that Mrgprs are novel itch receptors by directly sensing these compounds. Our data have shown the involvement of Mrgprs in mouse chronic itch models such as dry skin, contact dermatitis, and allergic itch. Importantly, some of the results have been confirmed in human psychophysical studies. In addition, we have genetically labeled and manipulated Mrgpr-expressing neurons in DRG and showed these neurons defined itch-mediating primary sensory neurons with specific projection pattern in the skin and electrophysiological properties. More importantly, characterization of Mrgpr A3+ neurons suggests that itch coding in the DRG is mediated by labeled line mechanism. Therefore, we believe that targeting Mrgprs may lead to novel treatment of chronic itch in the future.

关键词： itch DRG neurons Mrgprs GPCRs

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Is Pre-Dromal Diagnosis of Parkinson's Disease Possible?

Is Pre-Dromal Diagnosis of Parkinson's Disease Possible?

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Piu Chan Department of Neurobiology Neurology and GeriatricsXuanwu Hospital of Capital Medical University Parkinson Disease Center of Beijing Institute for Brain Disorders Beijing Key Laboratory on Parkinson's Disease

Parkinson's disease(PD) is a chronic debilitating disease characterized by the selective and progressive loss of nigrostriatal dopamine neurons. The mechanisms underlying the pathophysiology of this disease are not fully understood, and there is yet no cure to prevent the progressive loss of the neurons. It is known that by the time patients become symptomatic and were diagnosed with PD, 60-80% of the neurons in the substantia nigra pars compacta have been irreversibly lost for years, indicating the existence of a "pre-motor" stage. Therefore, early detection of PD is realizable, and in turn will improve disease management and enable potential neuroprotective therapies to be introduced at a stage when they would provide the greatest benefit. To achieve this goal, we undertook the initiative for discovery of biomarkers for PD. Efforts have been made to establish a national consortium and community longitudinal cohorts using standardized protocols for collection of clinical information and tissue samples. Genetic polymorphisms of susceptible genes for PD identified by GWAS and association studies were studied in these cohorts toinvestigate the association with an increased risk and their predictive value individually and collectively. Blood levels of alpha-synuclien oligomerization and antibody were measured. In addition, non-motor symptoms such as olfactory dysfunction, RBD, and depression were screened in elderly with risk genes for PD. Their values in predicting PD in Chinese will be discussed.

关键词： Parkinson's Disease,Pre-dromal,Biomarker,Prediction

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