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Targeting the noradrenergic system for anti-inflammatory and neuroprotective effects: implications for Parkinson's disease

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Neural Regeneration Research 2018年第8期13卷 1332-1337页

作者： Eoin O'Neill Andrew Harkin Neuropsychopharmacology Research Group School of Pharmacy and Pharmaceutical Sciences & Trinity College Institute of Neuroscience Trinity College

Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability may provide neuroprotection. Noradrenaline inhibits microglial activation and suppresses pro-inflamma- tory mediator production （e.g., tumor necrosis factor-a, interleukin-1β ＆ inducible nitric oxide synthase activity）, thus limiting the cytotoxicity of midbrain dopaminergic neurons in response to an inflamma- tory stimulus. Neighbouring astrocyte populations promote a neurotrophic environment in response to β2-adrenoceptor （β2-AR） stimulation via the production of growth factors （e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor ＆ glial cell derived neurotrophic factor which have shown promising neuroprotective and neuro-restorative effects in the nigrostriatal dopaminergic system. More recent findings have demonstrated a role for the β2-AR in down-regulating expression levels of the human a-synuclein gene SNCA and relative a-synuclein protein abundance. Given that a-synuclein is a major protein constituent of Lewy body pathology, a hallmark neuropathological feature in Parkinson＇s disease, these findings could open up new avenues for pharmacological intervention strategies aimed at alleviating the burden of a-synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed herein supports our hypothesis of a tripartite neuroprotective role for noradrenaline in combating PD-related neuropathology and motor dysfunction via （1） inhibiting nigral microglial activation ＆ pro-inflammatory mediator production, （2） promoting the synthesis of neurotrophic factors from midbrain astrocytes and （3） downregulating a-synuclein gene expression and protein abundance in a β2-AR-dependent manner. Thus, taken together, either pharmacologically enhancing extra-synaptic noradrenaline bioavailability or targeting glial β2-ARs direct

关键词： noradrenaline microglia astrocytes inflammation Parkinson's disease neuroprotection animalmodel dopamie

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Microglia-oligodendrocyte intercellular communication: role of extracellular vesicle lipids in functional signalling

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Neural Regeneration Research 2021年第6期16卷 1194-1195页

作者： Alice Gualerzi Marta Lombardi Claudia Verderio IRCCS Fondazione Don Carlo Gnocchi MilanItaly CNR institute of neuroscience MilanItaly

The term microglia refers to the group of resident brain immune-cells that are responsible,mainly,for the immune response and the homeostasis of the *** monocyte-derived macrophages that infiltrate the brain,microglia are longlived cells which arise exclusively from the embryonic yolk sac(Stratoulias et al.,2019).Impairment in microglia functions is at the basis for the development of multiple brain diseases,including multiple sclerosis and neurodegenerative *** the last decade,the number of research articles and reviews dealing with the role of microglia in the pathogenesis of brain disorders has exponentially increased.

关键词： al. homeostasis diseases

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Bridging the gap:axonal fusion drives rapid functional recovery of the nervous system

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Neural Regeneration Research 2018年第4期13卷 591-594页

作者： Jean-Sébastien Teoh Michelle Yu-Ying Wong Tarika Vijayaraghavan Brent Neumann neuroscience Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash University

Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently *** inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to *** to humans,a number of species possess far greater regenerative capabilities,and can therefore provide important insights into how our own nervous systems can be *** particular,several invertebrate species have been shown to rapidly initiate regeneration post-injury,allowing separated axon segments to *** process,known as axonal fusion,represents a highly efficient repair mechanism as a regrowing axon needs to only bridge the site of damage and fuse with its separated counterpart in order to re-establish its original *** recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged ***,we revealed the importance of injury-induced changes in the composition of the axonal membrane for mediating axonal fusion,and discovered that the level of axonal fusion can be enhanced by promoting a neuron＇s intrinsic growth potential.A complete understanding of the molecular mechanisms controlling axonal fusion may permit similar approaches to be applied in a clinical setting.

关键词： axonal fusion axon regeneration nervous system repair nerve injury phosphatidylserine functional repair axonal transport Caenorhabditis elegans

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Does Normobaric Hypoxic Resistance Training Confer Benefit over Normoxic Training in Athletes?A Narrative Review

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Journal of Science in Sport and Exercise 2022年第4期4卷 306-314页

作者： Louise Deldicque institute of neuroscience UCLouvainLouvain-la-NeuveBelgium

Purpose The aim of the present review was to focus on normobaric hypoxic resistance training and to discuss to what extent this method can be efficient for athletes to potentiate classical adaptations to resistance training and thereby *** Search terms related to the topic of the present review such as normobar*,hypox*,resistance exercise,resistance training and performance were inserted in Pubmed and *** total,16 articles made the core of this narrative *** Based on the available literature,2-3 sessions a week performed in hypoxic conditions for 4-6 weeks with a F_(i)O_(2)of 0.14-0.15 should recommended to athletes looking at potentiating the effects of resistance training.A large range of loads has been found to be efficient at inducing physiological effects in hypoxic vs normoxic conditions,from 20%to 90%of the ***,at least the last set should be performed to failure,if not ***,inter-set rest periods should be around 30 s for low-load exercise(30%-40%1-RM),around 60 s for moderate-load exercise(60%-70%1-RM)and 2 min for high-load exercise(85%-90%1-RM).Conclusion While there is no one size fits all and certainly no guarantee of added value over normoxic training,each athlete looking at potentiating the effects of resistance training should try to implement some sessions in hypoxic *** on the individual response,subtle improvements may be expected on muscle strength and mass,velocity and power,as well as hormonal responses to resistance training.

关键词： Muscle mass Strength F_(i)O_(2) Hypoxic chamber Performance

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Defective autophagy and Alzheimer’s disease: is calcium the key?

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Neural Regeneration Research 2019年第12期14卷 2081-2082页

作者： Riccardo Filadi Paola Pizzo Department of Biomedical Sciences University of Padua and Neuroscience Institute-Italian National Research Council (CNR)

Presenilins and autophagy: Presenilin 1 (PS1) and presenilin 2 (PS2) are homologous, multi-pass transmembrane proteins endowed with pleiotropic functions, ranging from the regulation of membrane trafficking to cell differentiation. Their catalytic activity within the γ-secretase complex, an aspartyl-protease responsible for the intramembrane cleavage of several different type I transmembrane proteins, has been intensively studied in the context of Alzheimer’s disease (AD). Indeed, tens of autosomal dominant mutations in the PSEN1 and PSEN2 genes (encoding PS1 and PS2, respectively) have been associated with the rare familial forms of AD (FAD).

关键词： Alzheimer is cell tens has PS1 PS2

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Development and transdifferentiation into inner hair cells require Tbx2

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National Science Review 2022年第12期9卷 135-148页

作者： Zhenghong Bi Xiang Li Minhui Ren Yunpeng Gu Tong Zhu Shuting Li Guangqin Wang Suhong Sun Yuwei Sun Zhiyong Liu institute of neuroscience State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology

Atohl is essential for the development of both outer hair cells(OHCs) and inner hair cells(IHCs) in the mammalian co *** Ikzf2 is necessary for OHC development,the key gene re quired for IHC development remains *** found that deletion of Tbx2 in neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% of IHC genes and inducing 56.3% of OHC genes,including *** importantly,persistent expression of Tbx2 coupled with transient Atohl expression effe ctively reprogrammed non-sensory supporting cells into new IHCs expressing the functional IHC marker *** differentiation status of these new IHCs was considerably more advanced than that previously ***,Tbx2 is essential for IHC development and co-upregulation of Tbx2 with Atohl in supporting cells represents a new approach for treating deafness related to IHC degeneration.

关键词： Tbx2 cochlea inner hair cell supporting cell Ikzf2 outer hair cell

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Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque

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neuroscience Bulletin 2024年第2期40卷 171-181页

作者： Lin Yang Min Jin Cong Zhang Ning Qian Mingsha Zhang Key Laboratory of Cognitive neuroscience and Learning Division of PsychologyBeijing Normal UniversityBeijing 100875China institute of neuroscience Key Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of neuroscience and Zuckerman institute Columbia UniversityNew York 10027USA

Even though retinal images of objects change their locations following each eye movement,we perceive a stable and continuous *** possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal *** have been several proposals on how this may be done,including eye-position modulation(gain fields)of retinotopic receptive fields(RFs)and craniotopic *** the present study,we investigated coordinate systems used by RFs in the lateral intraparietal(LIP)cortex and frontal eye fields(FEF)and compared the two *** mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate *** same recording and analysis procedures were applied to the two brain *** found that,in both areas,RFs were distributed from retinotopic to craniotopic *** was no significant difference between the distributions in the LIP and *** a small fraction of neurons was fully craniotopic,whereas most neurons were between the retinotopic and craniotopic *** distributions were strongly biased toward the retinotopic side but with significant craniotopic *** results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF,and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.

关键词： Reference frames Eye-centered Headcentered Visual stability

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Octopamine enhances learning

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National Science Review 2024年第6期11卷 82-83页

作者： Yvette E.Fisher Department of Molecular and Cell Biology and Helen Wills neuroscience institute University of California

Across the animal kingdom, diverse monoamines actuate and modulate neural circuit function. However, measuring the rapid dynamics of these neuromodulators at cellular resolution has historically presented significant ... 详细信息

关键词： learning enhances octopamine

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srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons by inactivating RAC1

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Asian Pacific Journal of Tropical Medicine 2014年第8期7卷 630-638页

作者： Quan-Peng Zhang Hai-Ying Zhang Xian-Fang Zhang Jiu-Hong Zhao Zhi-Jian Ma Dan Zhao Xi-Nan Yi Department of Anatomy Hainan Medical College neuroscience Research institute Hainan Medical College

Objective:To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion ***:In this study,expression of Slit1 was observed predominantly in the *** expression of Robo2 and srCAP3 was detected in sensory neurons of postnatal rat cultured dorsal root ganglion(DRG).Furthermore,upregulation of srGAP3 following sciatic nerve transection was detected by immunohistochemistry and Western ***:It was observed that inhibition of nenrite outgrowth in cultured adult DRG neurons following treatment with anti-srGAP3 or anti-Robo2 was more effectively(1.5-fold higher) than that following treatment with an anti-BDNF positive control *** demonstrated that srGAP3 interacted with Robo2 and Slit1 protein to decrease Rac1-CTP activity in cultured adult rat DRG neurons and the opposite effect on Rac1-GTP activity was detected by co-immunoprecipitation and immunoblotting analyses following treatment with anti-Robo2 or *** data demonstrated a role for srGAP3 in nenrite outgrowth ol DRG sensory ***:Our observations suggest that srGAP3 promotes neurile outgrowth and filopodial growth cones by interacting with Robo2 to inactivate Rac1 in mammalian DRG neurons.

关键词： Rats Dorsal root ganglion Slit-Robo GTPase activating protein 3

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Enterochromaffin Cell:Friend or Foe for Human Health?

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neuroscience Bulletin 2023年第11期39卷 1732-1734页

作者： Yang Yu Yong-Chang Li Fu-Chao Zhang Guang-Yin Xu Jiangsu Key Laboratory of Neuropsychiatric Diseases and institute of neuroscience Soochow UniversitySuzhou 215123China

Enterochromaffin(EC)cells are a type of enteroendocrine cells that reside in the epithelial lining of the gastrointestinal *** function as sensory transducers of stimuli present in the intestinal lumen,as afferent nerves do not protrude into the lumen,but have been shown to act as a friend or a foe depending on various *** has been well-described that EC cells play their role by releasing 5-HT to activate neighboring afferent nerves in a paracrine fashion,while emerging evidence suggests the existence of synaptic-like connections between enteroendocrine cells and adjacent afferent nerves based on in vitro co-culture and in vivo viral tracing studies.

关键词： nerves releasing Human

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