Motor Alterations Induced by Chronic 4-Aminopyridine Infusion in the Spinal Cord In vivo: Role of Glutamate and GABA Receptors

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

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In vivo two-photon imaging reveals a role of progesterone in reducing axonal dieback after spinal cord injury in mice

Neuropharmacology ◽

10.1016/j.neuropharm.2016.12.007 ◽

2017 ◽

Vol 116 ◽

pp. 30-37 ◽

Cited By ~ 8

Author(s):

Zhijie Yang ◽

Wenguang Xie ◽

Furong Ju ◽

Akbar khan ◽

Shengxiang Zhang

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Two Photon ◽

Cord Injury ◽

Photon Imaging ◽

Two Photon Imaging

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Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1922089117 ◽

2020 ◽

Vol 117 (30) ◽

pp. 18018-18028

Author(s):

Nira de la Vega Gallardo ◽

Rosana Penalva ◽

Marie Dittmer ◽

Michelle Naughton ◽

John Falconer ◽

...

Keyword(s):

Spinal Cord ◽

Ex Vivo ◽

Matricellular Protein ◽

Suprachiasmatic Nuclei ◽

Dynamic Expression ◽

Ccn3 Expression ◽

Cns Myelination

CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3−/−mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.

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Melatonin protects spinal cord injury by up-regulating IGFBP3 through the improvement of microcirculation in a rat model

RSC Advances ◽

10.1039/c9ra04591k ◽

2019 ◽

Vol 9 (55) ◽

pp. 32072-32080

Author(s):

Kun Wang ◽

Meng Li ◽

Linyu Jin ◽

Chao Deng ◽

Zhi Chen ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rat Model ◽

Cord Injury

The present study was aimed at the investigation of the effects of melatonin on spinal cord injury (SCI) and the role of IGFBP3 in SCI both in vivo and in vitro.

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Protective Effects of CISD2 and Influence of Curcumin on CISD2 Expression in Aged Animals and Inflammatory Cell Model

Nutrients ◽

10.3390/nu11030700 ◽

2019 ◽

Vol 11 (3) ◽

pp. 700 ◽

Cited By ~ 6

Author(s):

Chai-Ching Lin ◽

Tien-Huang Chiang ◽

Yu-Yo Sun ◽

Muh-Shi Lin

Keyword(s):

Spinal Cord ◽

Mitochondrial Dysfunction ◽

Cell Model ◽

Neural Cells ◽

Protective Effects ◽

Curcumin Treatment ◽

Cord Injury

Background: Inflammation and mitochondrial dysfunction have been linked to trauma, neurodegeneration, and aging. Impairment of CISD2 expression may trigger the aforementioned pathological conditions in neural cells. We previously reported that curcumin attenuates the downregulation of CISD2 in animal models of spinal cord injury and lipopolysaccharide (LPS)-treated neuronal cells. In this study, we investigate (1) the role of CISD2 and (2) how curcumin regulates CISD2 in the aging process. Materials and methods: The serial expression of CISD2 and the efficacy of curcumin treatment were evaluated in old (104 weeks) mice and long-term cultures of neural cells (35 days in vitro, DIV). LPS-challenged neural cells (with or without siCISD2 transfection) were used to verify the role of curcumin on CISD2 underlying mitochondrial dysfunction. Results: In the brain and spinal cord of mice aged P2, 8, 25, and 104 weeks, we observed a significant decrease in CISD2 expression with age. Curcumin treatment in vivo and in vitro was shown to upregulate CISD2 expression; attenuate inflammatory response in neural cells. Moreover, curcumin treatment elevated CISD2 expression levels and prevented mitochondrial dysfunction in LPS-challenged neural cells. The beneficial effects of curcumin in either non-stressed or LPS-challenged cells that underwent siCISD2 transfection were significantly lower than in respective groups of cells that underwent scrambled siRNA-transfection. Conclusions: We hypothesize that the protective effects of curcumin treatment in reducing cellular inflammation associated trauma, degenerative, and aging processes can be partially attributed to elevated CISD2 expression. We observed a reduction in the protective effects of curcumin against injury-induced inflammation and mitochondrial dysfunction in cells where CISD2 expression was reduced by siCISD2.

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Notch1 control of oligodendrocyte differentiation in the spinal cord

The Journal of Cell Biology ◽

10.1083/jcb.200202002 ◽

2002 ◽

Vol 158 (4) ◽

pp. 709-718 ◽

Cited By ~ 126

Author(s):

Stéphane Genoud ◽

Corinna Lappe-Siefke ◽

Sandra Goebbels ◽

Freddy Radtke ◽

Michel Aguet ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Transgenic Mice ◽

Oligodendrocyte Differentiation ◽

Temporal Regulation ◽

Development And Differentiation ◽

The Central Nervous System

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.

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Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

eLife ◽

10.7554/elife.47837 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Rebecca A Callahan ◽

Richard Roberts ◽

Mohini Sengupta ◽

Yukiko Kimura ◽

Shin-ichi Higashijima ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Speed Control ◽

Morphological Properties ◽

Larval Zebrafish ◽

Motor Circuits ◽

Transgenic Lines ◽

Left And Right

The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These V2b subclasses synapse directly onto motor neurons with differential targeting to speed-specific circuits. In vivo, optogenetic manipulation of V2b activity modulates locomotor frequency: suppressing V2b neurons elicits faster locomotion, whereas activating V2b neurons slows locomotion. We conclude that V2b neurons serve as a brake on axial motor circuits. Together, these results indicate a role for ipsilateral inhibition in speed control.

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Melatonin Alleviates Microglia-Mediated Neuroinflammation By Suppressing NLRP3 Inflammasome-Mediated Pyroptosis Via ROS/mtDNA/STING Pathway After Spinal Cord Injury

10.21203/rs.3.rs-716835/v1 ◽

2021 ◽

Author(s):

Jin Wang ◽

Haiyuan Yang ◽

Fan Zhang ◽

Minghao Shao ◽

Haocheng Xu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Nlrp3 Inflammasome ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation ◽

Cord Injury ◽

Sting Pathway

Abstract BackgroundMicroglia pyroptosis-induced neuroinflammation has been one of the potential treatment targets for spinal cord injury (SCI). And melatonin is reported to have anti-neuroinflammation effect on SCI, but the underlying mechanism is largely unexplored. In addition, the potential regulatory role of stimulator of interferon genes (STING) mediated innate immune response in the SCI-induced neuroinflammation also remains unknown. The aim of this study is to identify the potential molecular mechanism of the anti-neuroinflammation effect of melatonin in SCI mice and to explore whether STING-mediated signal pathway is involved in this pharmacological process. MethodsIn vivo, the C57BL/6 female mice underwent SCI injury or Sham surgery (laminectomy alone). Melatonin and selective STING antagonist C-176 were administered intraperitoneally after injury in the SCI group once a day for 3 or 28 consecutive days for different experiments. The BMS score system was adopted to assess the motor function of mice. In vitro, the Lipopolysaccharide (LPS)/ATP was combinedly used to induce cell pyroptosis in BV2 microglia and the adenovirus was used to overexpress STING. A series of molecular experiments including Western blot (WB), quantitative real-time polymerase chain reaction (RT-qPCR), enzyme linked immunosorbent assay (ELISA) and immunofluorescence (IF) were performed in vivo and in vitro. ResultsOur results showed that melatonin effectively suppressed NLRP3 inflammasome-induced pyroptosis and STING-mediated pathway after SCI. In addition, C-176 also alleviated the NLRP3 inflammasome-mediated pyroptosis and promoted functional recovery in vivo. In vitro, we also found that melatonin abrogated NLRP3 inflammasome activation in LPS/ATP-induced BV2 cells, while overexpression of STING reversed the anti-pyroptotic role of melatonin. Subsequent results together indicated that the role of melatonin on STING-dependent NLRP3 inflammasome activation may be mediated by decreasing ROS production and cytosolic mtDNA release. ConclusionThis study preliminarily demonstrated that melatonin exerts its anti-neuroinflammation role on SCI by alleviating the NLRP3 inflammasome-mediated pyroptosis, which was mediated by blocking the ROS/mtDNA/STING pathway. It provides us a better understanding of the pathological mechanism after SCI and offer experiment evidence to promote the use of melatonin for SCI.

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Sensory neurons contacting the cerebrospinal fluid require the Reissner fiber to detect spinal curvature in vivo

10.1101/861344 ◽

2019 ◽

Cited By ~ 1

Author(s):

Adeline Orts-Del’Immagine ◽

Yasmine Cantaut-Belarif ◽

Olivier Thouvenin ◽

Julian Roussel ◽

Asha Baskaran ◽

...

Keyword(s):

Spinal Cord ◽

Cerebrospinal Fluid ◽

Sensory Neurons ◽

Critical Role ◽

Central Canal ◽

Spinal Curvature ◽

List Type ◽

Close Vicinity

SummaryRecent evidence indicate active roles for the cerebrospinal fluid (CSF) on body axis development and morphogenesis of the spine implying CSF-contacting neurons (CSF-cNs) in the spinal cord. CSF-cNs project a ciliated apical extension into the central canal that is enriched in the channel PKD2L1 and enables the detection of spinal curvature in a directional manner. Dorsolateral CSF-cNs ipsilaterally respond to lateral bending while ventral CSF-cNs respond to longitudinal bending. Historically, the implication of the Reissner fiber (RF), a long extracellular thread in the CSF, to CSF-cN sensory functions has remained a subject of debate. Here, we reveal using electron microscopy in zebrafish larvae that the RF is in close vicinity with cilia and microvilli of ventral and dorsolateral CSF-cNs. We investigate in vivo the role of cilia and the Reissner fiber in the mechanosensory functions of CSF-cNs by combining calcium imaging with patch-clamp recordings. We show that disruption of cilia motility affects CSF-cN sensory responses to passive and active curvature of the spinal cord without affecting the Pkd2l1 channel activity. Since ciliary defects alter the formation of the Reissner fiber, we investigated whether the Reissner fiber contributes to CSF-cN mechanosensitivity in vivo. Using a hypomorphic mutation in the scospondin gene that forbids the aggregation of SCO-spondin into a fiber, we demonstrate in vivo that the Reissner fiber per se is critical for CSF-cN mechanosensory function. Our study uncovers that neurons contacting the cerebrospinal fluid functionally interact with the Reissner fiber to detect spinal curvature in the vertebrate spinal cord.Abstract FigureeToCThe role of the Reissner fiber, a long extracellular thread running in the cerebrospinal fluid (CSF), has been since its discovery in 1860 a subject of debate. Orts-Del’Immagine et al. report that the Reissner fiber plays a critical role in the detection of spinal curvature by sensory neurons contacting the CSF.HighlightsSince its discovery, the role of the Reissner fiber has long been a subject of debateMechanoreception in CSF-contacting neurons (CSF-cNs) in vivo requires the Reissner fiberCSF-cN apical extension is in close vicinity of the Reissner fiberCSF-cNs and the Reissner fiber form in vivo a sensory organ detecting spinal curvature

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