Diseases of the nervous system associated with calcium channelopathies

NARCIS (Netherlands)

Todorov, Boyan Bogdanov

2010-01-01

The aim of the studies described in this thesis was to investigate how abnormal CaV2.1 channel function can cause disease, in particular motor coordination dysfunction. The chapters illustrate how various neuronal cell types in the periphery (peripheral nervous system) and the central nervous system

Plasticity and Neural Stem Cells in the Enteric Nervous System

NARCIS (Netherlands)

Schaefer, Karl-Herbert; Van Ginneken, Chris; Copray, Sjef

2009-01-01

The enteric nervous system (ENS) is a highly organized part of the autonomic nervous system, which innervates the whole gastrointestinal tract by several interconnected neuronal networks. The ENS changes during development and keeps throughout its lifespan a significant capacity to adapt to

Glial Cells: The Other Cells of the Nervous System

Indian Academy of Sciences (India)

nervous system and that glial cells were a mere glue holding neurons in place, Schleich ... fact that these cells did not show any electrical activity like neurons or muscles ... membrane potential higher than that of the surrounding neu- rons.

Experimental alkylmercurial poisoning in swine. Lesions in the peripheral and central nervous systems

Energy Technology Data Exchange (ETDEWEB)

Charlton, K M

1974-01-01

The effects of alkylmercurial poisoning were studied in 16 pigs poisoned with daily oral doses of a fungicide containing methylmercury 2, 3-dihydroxy propyl mercaptide and methylmercury acetate. Clinical signs included weakness, wobbling gait, blindness, recumbency and death. Microscopic studies of the peripheral nervous system revealed Wallerian degeneration in sensory fibers and neuronal degeneration in dorsal root ganglia. In the central nervous system, there were neuronal degeneration of ischemic type, glial degeneration, gliosis and necrosis of the media of meningeal arterioles. The last mentioned lesion was not extensive. The sequential development of lesions and the absence of segmental demyelination suggest that the primary lesion in the peripheral nervous system was neuronal-axonal degeneration rather than degeneration of the Schwann cell and myelin sheath. 25 references.

Mesoscopic organization reveals the constraints governing Caenorhabditis elegans nervous system.

Directory of Open Access Journals (Sweden)

Raj Kumar Pan

Full Text Available One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. The coordination of many different co-occurring processes at this level underlies the command and control of overall network activity. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations such as, optimizing for resource constraints (viz., total wiring cost and communication efficiency (i.e., network path length. Even including information about the genetic relatedness of the cells cannot account for the observed modular structure. Comparison with other complex networks designed for efficient transport (of signals or resources implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including

Neuron-glia crosstalk in the autonomic nervous system and its possible role in the progression of metabolic syndrome: A new hypothesis

Directory of Open Access Journals (Sweden)

RODRIGO eDEL RIO

2015-12-01

Full Text Available Metabolic syndrome (MS is characterized by the following physiological alterations: increase in abdominal fat, insulin resistance, high concentration of triglycerides, low levels of HDL, high blood pressure and a generalized inflammatory state. One of the pathophysiological hallmarks of this syndrome is the presence of neurohumoral activation, which involve autonomic imbalance associated to hyperactivation of the sympathetic nervous system. Indeed, enhanced sympathetic drive has been linked to the development of endothelial dysfunction, hypertension, stroke, myocardial infarct and obstructive sleep apnea. Glial cells, the most abundant cells in the central nervous system, control synaptic transmission and regulate neuronal function by releasing bioactive molecules called gliotransmitters. Recently, a new family of plasma membrane channels called hemichannels has been described to allow the release of gliotransmitters and modulate neuronal firing rate. Moreover, a growing amount of evidence indicates that uncontrolled hemichannel opening could impair glial cell functions, affecting synaptic transmission and neuronal survival. Given that glial cell functions are disturbed in various metabolic diseases, we hypothesize that progression of MS may relies on hemichannel-dependent impairment of glial-to-neuron communication by a mechanism related to dysfunction of inflammatory response and mitochondrial metabolism of glial cells. In this manuscript, we discuss how glial cells may contribute to the enhanced sympathetic drive observed in MS, and shed light about the possible role of hemichannels in this process.

Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system.

Science.gov (United States)

Toth, Marton Lorant; Melentijevic, Ilija; Shah, Leena; Bhatia, Aatish; Lu, Kevin; Talwar, Amish; Naji, Haaris; Ibanez-Ventoso, Carolina; Ghose, Piya; Jevince, Angela; Xue, Jian; Herndon, Laura A; Bhanot, Gyan; Rongo, Chris; Hall, David H; Driscoll, Monica

2012-06-27

Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.

Mapping of neurons in the central nervous system of the guinea pig by use of antisera specific to the molluscan neuropeptide FMRFamide

DEFF Research Database (Denmark)

Triepel, J; Grimmelikhuijzen, C J

1984-01-01

Immunoreactive neurons were mapped in the central nervous system of colchicine-treated and untreated guinea pigs with the use of two antisera to the molluscan neuropeptide FMRFamide. These antisera were especially selected for their incapability to react with peptides of the pancreatic polypeptide...

Influence of thyroid in nervous system growth.

Science.gov (United States)

Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

2001-08-01

Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or

Macoilin, a conserved nervous system-specific ER membrane protein that regulates neuronal excitability.

Directory of Open Access Journals (Sweden)

Fausto Arellano-Carbajal

2011-03-01

Full Text Available Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O₂ responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca²(+ transients, at least in some neurons: in maco-1 mutants the O₂-sensing neuron PQR is unable to generate a Ca²(+ response to a rise in O₂. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O₂, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca²(+ channels, also fails to disrupt Ca²(+ responses in the PQR cell body to O₂ stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca²(+ channel α1 subunit, recapitulate the Ca²(+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or

Cellular changes in the enteric nervous system during ageing.

Science.gov (United States)

Saffrey, M Jill

2013-10-01

The intrinsic neurons of the gut, enteric neurons, have an essential role in gastrointestinal functions. The enteric nervous system is plastic and continues to undergo changes throughout life, as the gut grows and responds to dietary and other environmental changes. Detailed analysis of changes in the ENS during ageing suggests that enteric neurons are more vulnerable to age-related degeneration and cell death than neurons in other parts of the nervous system, although there is considerable variation in the extent and time course of age-related enteric neuronal loss reported in different studies. Specific neuronal subpopulations, particularly cholinergic myenteric neurons, may be more vulnerable than others to age-associated loss or damage. Enteric degeneration and other age-related neuronal changes may contribute to gastrointestinal dysfunction that is common in the elderly population. Evidence suggests that caloric restriction protects against age-associated loss of enteric neurons, but recent advances in the understanding of the effects of the microbiota and the complex interactions between enteric ganglion cells, mucosal immune system and intestinal epithelium indicate that other factors may well influence ageing of enteric neurons. Much remains to be understood about the mechanisms of neuronal loss and damage in the gut, although there is evidence that reactive oxygen species, neurotrophic factor dysregulation and/or activation of a senescence associated phenotype may be involved. To date, there is no evidence for ongoing neurogenesis that might replace dying neurons in the ageing gut, although small local sites of neurogenesis would be difficult to detect. Finally, despite the considerable evidence for enteric neurodegeneration during ageing, and evidence for some physiological changes in animal models, the ageing gut appears to maintain its function remarkably well in animals that exhibit major neuronal loss, indicating that the ENS has considerable

Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

Directory of Open Access Journals (Sweden)

Liu Kang-Jen

2011-01-01

Full Text Available Abstract Background Dystonia musculorum (dt is an autosomal recessive hereditary neuropathy with a characteristic uncoordinated movement and is caused by a defect in the bullous pemphigoid antigen 1 (BPAG1 gene. The neural isoform of BPAG1 is expressed in various neurons, including those in the central and peripheral nerve systems of mice. However, most previous studies on neuronal degeneration in BPAG1-deficient mice focused on peripheral sensory neurons and only limited investigation of the autonomic system has been conducted. Methods In this study, patterns of nerve innervation in cutaneous and iridial tissues were examined using general neuronal marker protein gene product 9.5 via immunohistochemistry. To perform quantitative analysis of the autonomic neuronal number, neurons within the lumbar sympathetic and parasympathetic ciliary ganglia were calculated. In addition, autonomic neurons were cultured from embryonic dt/dt mutants to elucidate degenerative patterns in vitro. Distribution patterns of neuronal intermediate filaments in cultured autonomic neurons were thoroughly studied under immunocytochemistry and conventional electron microscopy. Results Our immunohistochemistry results indicate that peripheral sensory nerves and autonomic innervation of sweat glands and irises dominated degeneration in dt/dt mice. Quantitative results confirmed that the number of neurons was significantly decreased in the lumbar sympathetic ganglia as well as in the parasympathetic ciliary ganglia of dt/dt mice compared with those of wild-type mice. We also observed that the neuronal intermediate filaments were aggregated abnormally in cultured autonomic neurons from dt/dt embryos. Conclusions These results suggest that a deficiency in the cytoskeletal linker BPAG1 is responsible for dominant sensory nerve degeneration and severe autonomic degeneration in dt/dt mice. Additionally, abnormally aggregated neuronal intermediate filaments may participate in

Optical imaging of neuronal activity and visualization of fine neural structures in non-desheathed nervous systems.

Directory of Open Access Journals (Sweden)

Christopher John Goldsmith

Full Text Available Locating circuit neurons and recording from them with single-cell resolution is a prerequisite for studying neural circuits. Determining neuron location can be challenging even in small nervous systems because neurons are densely packed, found in different layers, and are often covered by ganglion and nerve sheaths that impede access for recording electrodes and neuronal markers. We revisited the voltage-sensitive dye RH795 for its ability to stain and record neurons through the ganglion sheath. Bath-application of RH795 stained neuronal membranes in cricket, earthworm and crab ganglia without removing the ganglion sheath, revealing neuron cell body locations in different ganglion layers. Using the pyloric and gastric mill central pattern generating neurons in the stomatogastric ganglion (STG of the crab, Cancer borealis, we found that RH795 permeated the ganglion without major residue in the sheath and brightly stained somatic, axonal and dendritic membranes. Visibility improved significantly in comparison to unstained ganglia, allowing the identification of somata location and number of most STG neurons. RH795 also stained axons and varicosities in non-desheathed nerves, and it revealed the location of sensory cell bodies in peripheral nerves. Importantly, the spike activity of the sensory neuron AGR, which influences the STG motor patterns, remained unaffected by RH795, while desheathing caused significant changes in AGR activity. With respect to recording neural activity, RH795 allowed us to optically record membrane potential changes of sub-sheath neuronal membranes without impairing sensory activity. The signal-to-noise ratio was comparable with that previously observed in desheathed preparations and sufficiently high to identify neurons in single-sweep recordings and synaptic events after spike-triggered averaging. In conclusion, RH795 enabled staining and optical recording of neurons through the ganglion sheath and is therefore both a

Role of metallothionein-III following central nervous system damage

DEFF Research Database (Denmark)

Carrasco, Javier; Penkowa, Milena; Giralt, Mercedes

2003-01-01

We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area...... the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process....

Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

Science.gov (United States)

Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

2013-01-01

During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. PMID:23270605

Tachykinin-1 in the central nervous system regulates adiposity in rodents.

Science.gov (United States)

Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Yeo, Giles S H; Perez-Tilve, Diego

2015-05-01

Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

Identification of cholinergic synaptic transmission in the insect nervous system.

Science.gov (United States)

Thany, Steeve Hervé; Tricoire-Leignel, Hélène; Lapied, Bruno

2010-01-01

A major criteria initially used to localize cholinergic neuronal elements in nervous systems tissues that involve acetylcholine (ACh) as neurotransmitter is mainly based on immunochemical studies using choline acetyltransferase (ChAT), an enzyme which catalyzes ACh biosynthesis and the ACh degradative enzyme named acetylcholinesterase (AChE). Immunochemical studies using anti-ChAT monoclonal antibody have allowed the identification of neuronal processes and few types of cell somata that contain ChAT protein. In situ hybridization using cRNA probes to ChAT or AChE messenger RNA have brought new approaches to further identify cell bodies transcribing the ChAT or AChE genes. Combined application of all these techniques reveals a widespread expression of ChAT and AChE activities in the insect central nervous system and peripheral sensory neurons which implicates ACh as a key neurotransmitter. The discovery of the snake toxin alpha-bungatoxin has helped to identify nicotinic acetylcholine receptors (nAChRs). In fact, nicotine when applied to insect neurons, resulted in the generation of an inward current through the activation of nicotinic receptors which were blocked by alpha-bungarotoxin. Thus, insect nAChRs have been divided into two categories, sensitive and insensitive to this snake toxin. Up to now, the recent characterization and distribution pattern of insect nAChR subunits and the biochemical evidence that the insect central nervous system contains different classes of cholinergic receptors indicated that ACh is involved in several sensory pathways.

Brain-computer interface after nervous system injury.

Science.gov (United States)

Burns, Alexis; Adeli, Hojjat; Buford, John A

2014-12-01

Brain-computer interface (BCI) has proven to be a useful tool for providing alternative communication and mobility to patients suffering from nervous system injury. BCI has been and will continue to be implemented into rehabilitation practices for more interactive and speedy neurological recovery. The most exciting BCI technology is evolving to provide therapeutic benefits by inducing cortical reorganization via neuronal plasticity. This article presents a state-of-the-art review of BCI technology used after nervous system injuries, specifically: amyotrophic lateral sclerosis, Parkinson's disease, spinal cord injury, stroke, and disorders of consciousness. Also presented is transcending, innovative research involving new treatment of neurological disorders. © The Author(s) 2014.

Nanomedicine and the nervous system

CERN Document Server

Martin, Colin R; Hunter, Ross J

2012-01-01

The nanosciences encompass a variety of technologies ranging from particles to networks and nanostructures. Nanoparticles can be suitable carriers of therapeutic agents, and nanostructures provide suitable platforms and scaffolds for sub-micro bioengineering. This book focuses on nanomedicine and nanotechnology as applied to the nervous system and the brain. It covers nanoparticle-based immunoassays, nanofiber microbrush arrays, nanoelectrodes, protein nanoassemblies, nanoparticles-assisted imaging, nanomaterials, and ion channels. Additional topics include stem cell imaging, neuronal performa

Distribution and function of voltage-gated sodium channels in the nervous system.

Science.gov (United States)

Wang, Jun; Ou, Shao-Wu; Wang, Yun-Jie

2017-11-02

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.

Intrinsic cardiac nervous system in tachycardia induced heart failure.

Science.gov (United States)

Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

2003-11-01

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

Expression of Hepatoma-derived growth factor family members in the adult central nervous system

Directory of Open Access Journals (Sweden)

Abouzied Mekky M

2006-01-01

Full Text Available Abstract Background Hepatoma-derived growth factor (HDGF belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4 and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. Results HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. Conclusion The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells.

Cholinergic drugs as therapeutic tools in inflammatory diseases: participation of neuronal and non-neuronal cholinergic systems.

Science.gov (United States)

Sales, María Elena

2013-01-01

Acetylcholine (ACh) is synthesized by choline acetyltransferase (ChAT) from acetylcoenzime A and choline. This reaction occurs not only in pre-ganglionic fibers of the autonomic nervous system and post-ganglionic parasympathetic nervous fibers but also in non neuronal cells. This knowledge led to expand the role of ACh as a neurotransmitter and to consider it as a "cytotransmitter" and also to evaluate the existence of a non-neuronal cholinergic system comprising ACh, ChAT, acetylcholinesterase, and the nicotinic and muscarinic ACh receptors, outside the nervous system. This review analyzes the participation of cholinergic system in inflammation and discusses the role of different muscarinic and nicotinic drugs that are being used to treat skin inflammatory disorders, asthma, and chronic obstructive pulmonary disease as well as, intestinal inflammation and systemic inflammatory diseases, among others, to assess the potential application of these compounds as therapeutic tools.

Parallel simulation of axon growth in the nervous system

NARCIS (Netherlands)

J. Wensch; B.P. Sommeijer (Ben)

2002-01-01

textabstractIn this paper we discuss a model from neurobiology, which describes theoutgrowth of axons from neurons in the nervous system. The model combines ordinary differential equations, defining the movement of the axons, with parabolic partial differential equations. The parabolic equations

Restoring nervous system structure and function using tissue engineered living scaffolds

Institute of Scientific and Technical Information of China (English)

Laura A Struzyna; James P Harris; Kritika S Katiyar; H Isaac Chen; D KacyCullen

2015-01-01

Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner-vous system injury or neurodegenerative disease. Disconnection of axon pathways – the long-distance ifbers connecting specialized regions of the central nervous system or relaying peripheral signals – is a common feature of many neurological disorders and injury. However, functional axonal regenera-tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi-neered “living scaffolds”, which are preformed three-dimensional constructs consisting of living neural cells in a deifned, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration – mimicking key developmental mechanisms– or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

Restoring nervous system structure and function using tissue engineered living scaffolds

Directory of Open Access Journals (Sweden)

Laura A Struzyna

2015-01-01

Full Text Available Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

Some Central Nervous System Activities of Nerium Oleander Linn ...

African Journals Online (AJOL)

Erah

Nerium oleander Linn. on the central nervous system (CNS) of mice. Methods: The effect of the 50 % hydroalcohol extract of N. oleander flowers at dosage levels of 100 and 200 mg/kg ..... in the brain and inhibition of neuronal output could be ...

Peptides in the nervous systems of cnidarians: structure, function, and biosynthesis

DEFF Research Database (Denmark)

Grimmelikhuijzen, C J; Leviev, I; Carstensen, Kathrine

1996-01-01

Cnidarians are the lowest animal group having a nervous system and it was probably within this phylum or in a related ancestor group that nervous systems first evolved. The primitive nervous systems of cnidarians are strongly peptidergic. From a single sea anemone species, Anthopleura elegantissima...... molecule. In addition to well-known, "classical" processing enzymes, novel prohormone processing enzymes must be present in cnidarian neurons. These include a processing enzyme hydrolyzing at the C-terminal sides of acidic (Asp and Glu) residues and a dipeptidyl aminopeptidase digesting at the C......-terminal sides of N-terminally located X-Pro and X-Ala sequences. All this shows that the primitive nervous systems of cnidarians are already quite complex, and that neuropeptides play a central role in the physiology of these animals....

Gross anatomy and development of the peripheral nervous system.

Science.gov (United States)

Catala, Martin; Kubis, Nathalie

2013-01-01

The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS. Copyright © 2013 Elsevier B.V. All rights reserved.

Advances in Roles of miR-132 in the Nervous System

Directory of Open Access Journals (Sweden)

Yun Qian

2017-10-01

Full Text Available miR-132 is an endogenous small RNA and controls post-transcriptional regulation of gene expression via controlled degradation of mRNA or transcription inhibition. In the nervous system, miR-132 is significant for regulating neuronal differentiation, maturation and functioning, and widely participates in axon growth, neural migration, and plasticity. The miR-132 is affected by factors like mRNA expression, functional redundancy, and signaling cascades. It targets multiple downstream molecules to influence physiological and pathological neuronal activities. MiR-132 can influence the pathogenesis of many diseases, especially in the nervous system. The dysregulation of miR-132 results in the occurrence and exacerbation of neural developmental, degenerative diseases, like Alzheimer’s disease, Parkinson’s disease and epilepsy, neural infection and psychiatric disorders including disturbance of consciousness, cognition and memory, depression and schizophrenia. Regulation of miR-132 expression relieves symptoms, alleviates severity and finally effects a cure. This review aims to discuss the clinical potentials of miR-132 in the nervous system.

A neurochemical map of the developing amphioxus nervous system

Directory of Open Access Journals (Sweden)

Candiani Simona

2012-06-01

Full Text Available Abstract Background Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates, the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. Results By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify discrete groups of GABAergic and glutamatergic interneurons and cholinergic motoneurons at the level of the primary motor center (PMC, the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. Conclusions In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons.

The Emerging Roles for Telomerase in the Central Nervous System

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Meng-Ying Liu

2018-05-01

Full Text Available Telomerase, a specialized ribonucleoprotein enzyme complex, maintains telomere length at the 3′ end of chromosomes, and functions importantly in stem cells, cancer and aging. Telomerase exists in neural stem cells (NSCs and neural progenitor cells (NPCs, at a high level in the developing and adult brains of humans and rodents. Increasing studies have demonstrated that telomerase in NSCs/NPCs plays important roles in cell proliferation, neuronal differentiation, neuronal survival and neuritogenesis. In addition, recent works have shown that telomerase reverse transcriptase (TERT can protect newborn neurons from apoptosis and excitotoxicity. However, to date, the link between telomerase and diseases in the central nervous system (CNS is not well reviewed. Here, we analyze the evidence and summarize the important roles of telomerase in the CNS. Understanding the roles of telomerase in the nervous system is not only important to gain further insight into the process of the neural cell life cycle but would also provide novel therapeutic applications in CNS diseases such as neurodegenerative condition, mood disorders, aging and other ailments.

Localization of Reversion-Induced LIM Protein (RIL) in the Rat Central Nervous System

International Nuclear Information System (INIS)

Iida, Yuko; Matsuzaki, Toshiyuki; Morishima, Tetsuro; Sasano, Hiroshi; Asai, Kiyofumi; Sobue, Kazuya; Takata, Kuniaki

2009-01-01

Reversion-induced LIM protein (RIL) is a member of the ALP (actinin-associated LIM protein) subfamily of the PDZ/LIM protein family. RIL serves as an adaptor protein and seems to regulate cytoskeletons. Immunoblotting suggested that RIL is concentrated in the astrocytes in the central nervous system. We then examined the expression and localization of RIL in the rat central nervous system and compared it with that of water channel aquaporin 4 (AQP4). RIL was concentrated in the cells of ependyma lining the ventricles in the brain and the central canal in the spinal cord. In most parts of the central nervous system, RIL was expressed in the astrocytes that expressed AQP4. Double-labeling studies showed that RIL was concentrated in the cytoplasm of astrocytes where glial fibrillary acidic protein was enriched as well as in the AQP4-enriched regions such as the endfeet or glia limitans. RIL was also present in some neurons such as Purkinje cells in the cerebellum and some neurons in the brain stem. Differential expression of RIL suggests that it may be involved in the regulation of the central nervous system

Neuronal chemokines : Versatile messengers in central nervous system cell interaction

NARCIS (Netherlands)

de Haas, A. H.; van Weering, H. R. J.; de Jong, E. K.; Boddeke, H. W. G. M.; Biber, K. P. H.

2007-01-01

Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS),

PET and SPET tracers for mapping the cardiac nervous system

International Nuclear Information System (INIS)

Langer, Oliver; Halldin, Christer

2002-01-01

The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[ 18 F]fluorodopamine, (-)-6-[ 18 F]fluoronorepinephrine and (-)-[ 11 C]epinephrine, and radiolabelled catecholamine analogues, such as [ 123 I]meta-iodobenzylguanidine, [ 11 C]meta-hydroxyephedrine, [ 18 F]fluorometaraminol, [ 11 C]phenylephrine and meta-[ 76 Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[ 18 F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility for cardiac neuronal imaging. (orig.)

Microglia - insights into immune system structure, function, and reactivity in the central nervous system

DEFF Research Database (Denmark)

Wirenfeldt, Martin; Babcock, Alicia A; Vinters, Harry V

2011-01-01

Microglia are essential cellular components of a well-functioning central nervous system (CNS). The development and establishment of the microglial population differs from the other major cell populations in the CNS i.e. neurons and macroglia (astrocytes and oligodendrocytes). This different onto...

PET imaging of the autonomic nervous system

International Nuclear Information System (INIS)

THACKERAY, James T.; BENGEL, Frank M.

2016-01-01

The autonomic nervous system is the primary extrinsic control of heart rate and contractility, and is subject to adaptive and maladaptive changes in cardiovascular disease. Consequently, noninvasive assessment of neuronal activity and function is an attractive target for molecular imaging. A myriad of targeted radiotracers have been developed over the last 25 years for imaging various components of the sympathetic and parasympathetic signal cascades. While routine clinical use remains somewhat limited, a number of larger scale studies in recent years have supplied momentum to molecular imaging of autonomic signaling. Specifically, the findings of the ADMIRE HF trial directly led to United States Food and Drug Administration approval of 123I-metaiodobenzylguanidine (MIBG) for Single Photon Emission Computed Tomography (SPECT) assessment of sympathetic neuronal innervation, and comparable results have been reported using the analogous PET agent 11C-meta-hydroxyephedrine (HED). Due to the inherent capacity for dynamic quantification and higher spatial resolution, regional analysis may be better served by PET. In addition, preliminary clinical and extensive preclinical experience has provided a broad foundation of cardiovascular applications for PET imaging of the autonomic nervous system. Recent years have witnessed the growth of novel quantification techniques, expansion of multiple tracer studies, and improved understanding of the uptake of different radiotracers, such that the transitional biology of dysfunctional subcellular catecholamine handling can be distinguished from complete denervation. As a result, sympathetic neuronal molecular imaging is poised to play a role in individualized patient care, by stratifying cardiovascular risk, visualizing underlying biology, and guiding and monitoring therapy.

Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

Science.gov (United States)

De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

2017-10-12

Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

Metallothionein expression in the central nervous system of multiple sclerosis patients

DEFF Research Database (Denmark)

Penkowa, M; Espejo, C; Ortega-Aznar, A

2003-01-01

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS...

Neurotropic Enterovirus Infections in the Central Nervous System.

Science.gov (United States)

Huang, Hsing-I; Shih, Shin-Ru

2015-11-24

Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

Neurotropic Enterovirus Infections in the Central Nervous System

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Hsing-I Huang

2015-11-01

Full Text Available Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

Effects of the Autonomic Nervous System, Central Nervous System ...

African Journals Online (AJOL)

The gastrointestinal tract is chiefly involved in the digestion of ingested food, facilitation of absorption process and expulsion of the undigested food material through motility process. Motility is influenced by neurohormonal system which is associated with the enteric nervous system , autonomic nervous system and the ...

Regulation of lipid metabolism by energy availability: a role for the central nervous system.

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Nogueiras, R; López, M; Diéguez, C

2010-03-01

The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

Cholinergic, serotoninergic and peptidergic components of the nervous system of Discocotyle sagittata (Monogenea:Polyopisthocotylea).

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Cable, J; Marks, N J; Halton, D W; Shaw, C; Johnston, C F; Tinsley, R C; Gannicott, A M

1996-12-01

Cholinergic, serotoninergic (5-HT) and peptidergic neuronal pathways have been demonstrated in both central and peripheral nervous systems of adult Discocotyle sagittata, using enzyme histochemistry and indirect immunocytochemistry in conjunction with confocal scanning laser microscopy. Antisera to 2 native flatworm neuropeptides, neuropeptide F and the FMRFamide-related peptide (FaRP), GNFFRFamide, were employed to detect peptide immunoreactivity. The CNS is composed of paired cerebral ganglia and connecting dorsal commissure, together with several paired longitudinal nerve cords. The main longitudinal nerve cords (lateral, ventral and dorsal) are interconnected at intervals by a series of annular cross-connectives, producing a ladder-like arrangement typical of the platyhelminth nervous system. At the level of the haptor, the ventral cords provide nerve roots which innervate each of the 9 clamps. Cholinergic and peptidergic neuronal organisation was similar, but distinct from that of the serotoninergic components. The PNS and reproductive system are predominantly innervated by peptidergic neurones.

Brain Facts: A Primer on the Brain and Nervous System.

Science.gov (United States)

Carey, Joseph, Ed.

This booklet describes only a glimpse of what is known about the nervous system, brain disorders, and the exciting avenues of research that promise new therapies for many of the most devastating neurological and psychiatric diseases. The neuron, brain development, sensation and perception, learning and memory, movement, advances and challenges in…

Widespread transduction of astrocytes and neurons in the mouse central nervous system after systemic delivery of a self-complementary AAV-PHP.B vector.

Science.gov (United States)

Rincon, Melvin Y; de Vin, Filip; Duqué, Sandra I; Fripont, Shelly; Castaldo, Stephanie A; Bouhuijzen-Wenger, Jessica; Holt, Matthew G

2018-04-01

Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher efficiency. We investigated how much we could boost CNS transgene expression by using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or scAAV2/PHP.B-GFP at equivalent doses. Three weeks postinjection, transgene expression was assessed in brain and spinal cord. We consistently observed more widespread CNS transduction and higher levels of transgene expression when using the scAAV2/PHP.B-GFP vector. In particular, we observed an unprecedented level of astrocyte transduction in the cortex, when using a ubiquitous CBA promoter. In comparison, neuronal transduction was much lower than previously reported. However, strong neuronal expression (including spinal motor neurons) was observed when the human synapsin promoter was used. These findings constitute the first reported use of an AAV-PHP.B capsid, encapsulating a scAAV genome, for gene transfer in adult mice. Our results underscore the potential of this AAV construct as a platform for safer and more efficacious gene therapy vectors for the CNS.

[3H]-2-Deoxyglucose autoradiography in a molluscan nervous system

International Nuclear Information System (INIS)

Reingold, S.C.; Sejnowski, T.J.; Gelperin, A.

1981-01-01

The authors have used [ 3 H]2-deoxyglucose autoradiography to correlate the labeling of individual neurons with electrical activity within the central nervous system of a terrestrial mollusc, Limax maximus. In an electrically quiescent control preparation where a single neuron is impaled with a glass microelectrode but not stimulated, several somata are uniformly labeled at 3-5 times background. In preparations where a single cell is impaled and stimulated, one or more somata are heavily labeled with [ 3 H]2-deoxyglucose at 10-50 times tissue background. This technique may be useful for surveying metabolically active neurons during spontaneous and driven electrical activity. (Auth.)

Transgenic tools to characterize neuronal properties of discrete populations of zebrafish neurons.

Science.gov (United States)

Satou, Chie; Kimura, Yukiko; Hirata, Hiromi; Suster, Maximiliano L; Kawakami, Koichi; Higashijima, Shin-ichi

2013-09-01

The developing nervous system consists of a variety of cell types. Transgenic animals expressing reporter genes in specific classes of neuronal cells are powerful tools for the study of neuronal network formation. We generated a wide variety of transgenic zebrafish that expressed reporter genes in specific classes of neurons or neuronal progenitors. These include lines in which neurons of specific neurotransmitter phenotypes expressed fluorescent proteins or Gal4, and lines in which specific subsets of the dorsal progenitor domain in the spinal cord expressed fluorescent proteins. Using these, we examined domain organization in the developing dorsal spinal cord, and found that there are six progenitor domains in zebrafish, which is similar to the domain organization in mice. We also systematically characterized neurotransmitter properties of the neurons that are produced from each domain. Given that reporter gene expressions occurs in a wide area of the nervous system in the lines generated, these transgenic fish should serve as powerful tools for the investigation of not only the neurons in the dorsal spinal cord but also neuronal structures and functions in many other regions of the nervous system.

The Central Nervous System Sites Mediating the Orexigenic Actions of Ghrelin

Science.gov (United States)

Mason, B.L.; Wang, Q.; Zigman, J.M.

2014-01-01

The peptide hormone ghrelin is important for both homeostatic and hedonic eating behaviors, and its orexigenic actions occur mainly via binding to the only known ghrelin receptor, the growth hormone secretagogue receptor (GHSR). GHSRs are located in several distinct regions of the central nervous system. This review discusses those central nervous system sites that have been found to play critical roles in the orexigenic actions of ghrelin, including hypothalamic nuclei, the hippocampus, the amygdala, the caudal brain stem, and midbrain dopaminergic neurons. Hopefully, this review can be used as a stepping stone for the reader wanting to gain a clearer understanding of the central nervous system sites of direct ghrelin action on feeding behavior, and as inspiration for future studies to provide an even-more-detailed map of the neurocircuitry controlling eating and body weight. PMID:24111557

The role of oxidative stress in nervous system aging.

Directory of Open Access Journals (Sweden)

Catrina Sims-Robinson

Full Text Available While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1(-/- mice, a mouse model of increased oxidative stress. Sod1(-/- mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1(+/+ mice at 30 months and the Sod1(-/- mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.

The role of oxidative stress in nervous system aging.

Science.gov (United States)

Sims-Robinson, Catrina; Hur, Junguk; Hayes, John M; Dauch, Jacqueline R; Keller, Peter J; Brooks, Susan V; Feldman, Eva L

2013-01-01

While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1(-/-)) mice, a mouse model of increased oxidative stress. Sod1(-/-) mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1(+/+) mice at 30 months and the Sod1(-/-) mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.

A theoretical model of naturally occurring cell death in the nervous system

OpenAIRE

Galli, Resta; Resta, Giovanni

1991-01-01

Throughout the animal kingdom, the formation of the nervous system involves the elimination of many cells, soon after their generation. This phenomenon, known as naturally occurring cell death, has precise time schedules, is observed in the vast majority of nervous structures and causes the 1oss of 15 - 85% of the neurones generated initially. Elimination of erroneous projections, as well as proper size matching between connecting structures can be achieved through cell death. However if elim...

Central Nervous System Vasculitis

Science.gov (United States)

... of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

Non-viral Nucleic Acid Delivery Strategies to the Central Nervous System

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James-Kevin Tan

2016-11-01

Full Text Available With an increased prevalence and understanding of central nervous system injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the central nervous system and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection, and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the central nervous system are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for central nervous system applications and will ultimately bring non-viral vectors closer to clinical application.

Autonomic Nervous System Disorders

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Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

Ontogeny of pioneer neurons in the antennal nervous system of the grasshopper Schistocerca gregaria.

Science.gov (United States)

Boyan, George; Ehrhardt, Erica

2017-01-01

The nervous system of the antenna of the grasshopper Schistocerca gregaria consists of two nerve tracts in which sensory cells project their axons to the brain. Each tract is pioneered early in embryogenesis by a pair of identified cells located apically in the antennal lumen. The pioneers are thought to originate in the epithelium of the antenna and then delaminate into the lumen where they commence axogenesis. However, unambiguous molecular identification of these cells in the epithelium, of an identifiable precursor, and of their mode of generation has been lacking. In this study, we have used immunolabeling against neuron-specific horseradish peroxidase and against Lachesin, a marker for differentiating epithelial cells, in combination with the nuclear stain DAPI, to identify the pioneers within the epithelium of the early embryonic antenna. We then track their delamination into the lumen as differentiated neurons. The pioneers are not labeled by the mesodermal/mesectodermal marker Mes3, consistent with an epithelial (ectodermal) origin. Intracellular dye injection, as well as labeling against the mitosis marker phospho-histone 3, identifies precursor cells in the epithelium, each associated with a column of cells. Culturing with the S-phase label 5-ethynyl-2'-deoxyuridine (EdU) shows that both a precursor and its column have incorporated the label, confirming a lineage relationship. Each set of pioneers can be shown to belong to a separate lineage of such epithelial cells, and the precursors remain and are proliferative after generating the pioneers. Analyses of mitotic spindle orientation then enable us to propose a model in which a precursor generates its pioneers asymmetrically via self-renewal.

Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

Science.gov (United States)

Meffre, Delphine; Grenier, Julien; Bernard, Sophie; Courtin, Françoise; Dudev, Todor; Shackleford, Ghjuvan'Ghjacumu; Jafarian-Tehrani, Mehrnaz; Massaad, Charbel

2014-04-01

Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.

The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

Science.gov (United States)

Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

2017-09-01

The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few

Central nervous system

Science.gov (United States)

The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

Calcium signal communication in the central nervous system.

Science.gov (United States)

Braet, Katleen; Cabooter, Liesbet; Paemeleire, Koen; Leybaert, Luc

2004-02-01

The communication of calcium signals between cells is known to be operative between neurons where these signals integrate intimately with electrical and chemical signal communication at synapses. Recently, it has become clear that glial cells also exchange calcium signals between each other in cultures and in brain slices. This communication pathway has received utmost attention since it is known that astrocytic calcium signals can be induced by neuronal stimulation and can be communicated back to the neurons to modulate synaptic transmission. In addition to this, cells that are generally not considered as brain cells become progressively incorporated in the picture, as astrocytic calcium signals are reported to be communicated to endothelial cells of the vessel wall and can affect smooth muscle cell tone to influence the vessel diameter and thus blood flow. We review the available evidence for calcium signal communication in the central nervous system, taking into account a basic functional unit -the brain cell tripartite- consisting of neurons, glial cells and vascular cells and with emphasis on glial-vascular calcium signaling aspects.

Features of the nervous system lesion in primary hypothyroidism (literature review

Directory of Open Access Journals (Sweden)

I.I. Bilous

2018-03-01

Full Text Available The review presents the pathogenetic mechanisms of central and peripheral nervous system pathology in primary hypothyroidism. Lack of thyroid hormones leads to changes in the organization of the central nervous system, decrease in the energy supply of neurons, changes in the synthesis of some specific proteins of the nervous system that cause the development of cretinism in children. The role of hypothyroidism in the development of cognitive impairment in adults, such as decreased cognitive function, memory and attention, has been proved. The impairment of logical thinking is found already in patients with subclinical hypothyroidism. Disorders in mediation exchange lead to the development of depression. Neuromuscular disorders (hypothyroid myopathy and myotonic phenomenon and affection to the peripheral nerves are best studied in hypothyroidism. Primary hypothyroidism may be masked by tunnel neuropathy, polyneuropathy and atactic syndrome. Despite the existing papers on the problem of hypothyroidism and its neurological complications, some issues of pathogenesis, diagnosis, course and treatment of neurological pathology in primary hypothyroidism require further research.

The Role of Oxidative Stress in Nervous System Aging

Science.gov (United States)

Sims-Robinson, Catrina; Hur, Junguk; Hayes, John M.; Dauch, Jacqueline R.; Keller, Peter J.; Brooks, Susan V.; Feldman, Eva L.

2013-01-01

While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1−/−) mice, a mouse model of increased oxidative stress. Sod1−/− mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1+/+ mice at 30 months and the Sod1−/− mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging. PMID:23844146

Spectral Mixing in Nervous Systems: Experimental Evidenceand Biologically Plausible Circuits

Science.gov (United States)

Kleinfeld, D.; Mehta, S. B.

The ability to compute the difference frequency for two periodic signals depends on a nonlinear operation that mixes those signals. Behavioral and psychophysical evidence suggest that such mixing is likely to occur in the vertebrate nervous system as a means to compare rhythmic sensory signals, such as occurs in human audition, and as a means to lock an intrinsic rhythm to a sensory input. Electrophysiological data from electroreceptors in the immobilized electric fish and somatosensory cortex in the anesthetized rat yield direct evidence for such mixing, providing a neurological substrate for the modulation and demodulation of rhythmic neuronal signals. We consider an analytical model of spectral mixing that makes use of the threshold characteristics of neuronal firing and which has features consistent with the experimental observations. This model serves as a guide for constructing circuits that isolate given mixture components. In particular, such circuits can generate nearly pure difference tones from sinusoidal inputs without the use of band-pass filters, in analogy to an image-reject mixer in communications engineering. We speculate that such computations may play a role in coding of sensory input and feedback stabilization of motor output in nervous systems.

Is Ghrelin Synthesized in the Central Nervous System?

Science.gov (United States)

Cabral, Agustina; López Soto, Eduardo J; Epelbaum, Jacques; Perelló, Mario

2017-03-15

Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

Is Ghrelin Synthesized in the Central Nervous System?

Directory of Open Access Journals (Sweden)

Agustina Cabral

2017-03-01

Full Text Available Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a, and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

Parkinson disease: the enteric nervous system spills its guts.

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Derkinderen, P; Rouaud, T; Lebouvier, T; Bruley des Varannes, S; Neunlist, M; De Giorgio, R

2011-11-08

Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as "the brain in the gut" because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders.

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

Science.gov (United States)

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates

International Nuclear Information System (INIS)

Jacob, M.H.

1984-01-01

The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by [ 3 H]thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with [ 3 H]thymidine for 24 or 48 hr and were subsequently sampled at specific intervals throughout the life cycle. I found that proliferative zones, consisting of columnar and placodal ectodermal cells, are established in regions of the body wall adjacent to underlying mesodermal cells. Mitosis in the proliferative zones generates a population of cells which leave the surface and migrate inward to join the nearby forming ganglia. Tracing specific [ 3 H]thymidine-labeled cells from the body wall to a particular ganglion and within the ganglion over time suggests that the final genomic replication of the neuronal precursors occurs before the cells join the ganglion while glial cell precursors and differentiating glial cells continue to divide within the ganglion for some time. Ultrastructural examination of the morphological features of the few mitosing cells observed within the Aplysia central nervous system supports this interpretation. The pattern of neurogenesis in the Aplysia central nervous system resembles the proliferation of cells in the neural tube and the migration of neural crest and ectodermal placode cells in the vertebrate nervous system but differs from the pattern described for other invertebrates

αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function.

Science.gov (United States)

Huang, Claire Yu-Mei; Zhang, Chuansheng; Ho, Tammy Szu-Yu; Oses-Prieto, Juan; Burlingame, Alma L; Lalonde, Joshua; Noebels, Jeffrey L; Leterrier, Christophe; Rasband, Matthew N

2017-11-22

Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility to neurons and to participate in ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons consist of diverse β subunits and αII spectrin. Although αII spectrin is found in neurons in both axonal and somatodendritic domains, using proteomics, biochemistry, and superresolution microscopy, we show that αII and βIV spectrin interact and form a periodic AIS cytoskeleton. To determine the role of spectrins in the nervous system, we generated Sptan1 f/f mice for deletion of CNS αII spectrin. We analyzed αII spectrin-deficient mice of both sexes and found that loss of αII spectrin causes profound reductions in all β spectrins. αII spectrin-deficient mice die before 1 month of age and have disrupted AIS and many other neurological impairments including seizures, disrupted cortical lamination, and widespread neurodegeneration. These results demonstrate the importance of the spectrin cytoskeleton both at the AIS and throughout the nervous system. SIGNIFICANCE STATEMENT Spectrin cytoskeletons play diverse roles in neurons, including assembly of excitable domains such as the axon initial segment (AIS) and nodes of Ranvier. However, the molecular composition and structure of these cytoskeletons remain poorly understood. Here, we show that αII spectrin partners with βIV spectrin to form a periodic cytoskeleton at the AIS. Using a new αII spectrin conditional knock-out mouse, we show that αII spectrin is required for AIS assembly, neuronal excitability, cortical lamination, and to protect against neurodegeneration. These results demonstrate the broad importance of spectrin cytoskeletons for nervous system function and development and have important implications for nervous system injuries and diseases because disruption of the spectrin cytoskeleton is a common molecular pathology. Copyright © 2017 the authors 0270-6474/17/3711311-12$15.00/0.

Neuronal Migration Disorders

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... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

NeuronBank: a tool for cataloging neuronal circuitry

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Paul S Katz

2010-04-01

Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

Overview of the Autonomic Nervous System

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... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

Pluralistic roles for glycogen in the central and peripheral nervous systems.

Science.gov (United States)

Fryer, Kirsty L; Brown, Angus M

2015-02-01

Glycogen is present in the mammalian nervous system, but at concentrations of up to one hundred times lower than those found in liver and skeletal muscle. This relatively low concentration has resulted in neglect of assigning a role(s) for brain glycogen, but in the last 15 years enormous progress has been made in revealing the multifaceted roles that glycogen plays in the mammalian nervous system. Initial studies highlighted a role for glycogen in supporting neural elements (neurons and axons) during aglycemia, where glycogen supplied supplementary energy substrate in the form of lactate to fuel neural oxidative metabolism. The appropriate enzymes and membrane bound transporters have been localized to cellular locations consistent with astrocyte to neuron energy substrate shuttling. A role for glycogen in supporting the induction of long term potential (LTP) in the hippocampus has recently been described, where glycogen is metabolized to lactate and shuttled to neurons via the extracellular space by monocarboxylate transporters, where it plays an integral role in the induction process of LTP. This is the first time that glycogen has been assigned a role in a distinct, complex physiological brain function, where the lack of glycogen, in the presence of normoglycemia, results in disturbance of the function. The signalling pathway that alerts astrocytes to increased neuronal activity has been recently described, highlighting a pivotal role for increased extracellular potassium ([K(+)]o) that routinely accompanies increased neural activity. An astrocyte membrane bound bicarbonate transporter is activated by the [K(+)]o, the resulting increase in intracellular bicarbonate alkalizing the cell's interior and activating soluble adenyl cyclase (sAC). The sAC promotes glycogenolysis via increases in cyclic AMP, ultimately producing lactate, which is shuttled out of the astrocyte and presumably taken up by neurons from the extracellular space.

Model of Artificial Intelligence Medium and its Use in Treating Disorders of the Nervous System

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Shumilov Vladimir

2016-01-01

Full Text Available The work is devoted to modeling of the nervous system, the brain. The article considers the mechanism of formation of event traces fixed in the brain in the form of connections between neurons and the effect of these traces on the later passage of signals through the brain. That is, the influence of experience (traces of previous events on the organism’s reaction by forecasting upcoming events. This «forecast» and anticipatory avoidance of dangers based on traces of previous events makes the nervous system, the brain useful for the organism, for its survival and expansion. The author proposes to use a computational model of the brain to study disorders of the nervous system, brain, and make recommendations for their prevention.

Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System.

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Ren, Xiaoyuan; Zou, Lili; Zhang, Xu; Branco, Vasco; Wang, Jun; Carvalho, Cristina; Holmgren, Arne; Lu, Jun

2017-11-01

The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high-energy demand. These two disulfide reductase systems are active in various areas of the brain and are considered to be critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins. The Trx and GSH systems, which reversibly regulate thiol modifications, regulate redox signaling involved in various biological events in the CNS. In this review, we focus on the following: (i) how ROS/RNS are produced and mediate signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and GSH systems causes alterations of cellular redox signaling in human neuronal diseases; and (iv) the effects of certain small molecules that target thiol-based signaling pathways in the CNS. Further study on the roles of thiol-dependent redox systems in the CNS will improve our understanding of the pathogenesis of many human neuronal disorders and also help to develop novel protective and therapeutic strategies against neuronal diseases. Antioxid. Redox Signal. 27, 989-1010.

Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

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Kurt F. Hauser

2018-01-01

Full Text Available The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System.

Science.gov (United States)

Hauser, Kurt F; Knapp, Pamela E

2017-01-01

The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS) regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance) during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

FMRFamide-like immunoreactivity in the central nervous system of the cephalopod mollusc, Idiosepius notoides

DEFF Research Database (Denmark)

Wollesen, Tim; Loesel, R.; Wanninger, Andreas Wilhelm Georg

2008-01-01

For more than a century, cephalopod molluscs have been the subject of extensive studies with respect to their complex neuroanatomy and behavior. In comparison to gastropod molluscs surprisingly little work has been carried out on the characterization of neurons in the central nervous system (CNS...

Cell Death, Neuronal Plasticity and Functional Loading in the Development of the Central Nervous System

Science.gov (United States)

Keefe, J. R.

1985-01-01

Research on the precise timing and regulation of neuron production and maturation in the vestibular and visual systems of Wistar rats and several inbred strains of mice (C57B16 and Pallid mutant) concentrated upon establishing a timing baseline for mitotic development of the neurons of the vestibular nuclei and the peripheral vestibular sensory structures (maculae, cristae). This involved studies of the timing and site of neuronal cell birth and preliminary studies of neuronal cell death in both central and peripheral elements of the mammalian vestibular system. Studies on neuronal generation and maturation in the retina were recently added to provide a mechanism for more properly defining the in utero' developmental age of the individual fetal subject and to closely monitor potential transplacental effects of environmentally stressed maternal systems. Information is given on current efforts concentrating upon the (1) perinatal period of development (E18 thru P14) and (2) the role of cell death in response to variation in the functional loading of the vestibular and proprioreceptive systems in developing mammalian organisms.

A cellular and regulatory map of the cholinergic nervous system of C. elegans

Science.gov (United States)

Pereira, Laura; Kratsios, Paschalis; Serrano-Saiz, Esther; Sheftel, Hila; Mayo, Avi E; Hall, David H; White, John G; LeBoeuf, Brigitte; Garcia, L Rene; Alon, Uri; Hobert, Oliver

2015-01-01

Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.12432.001 PMID:26705699

Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II.

Science.gov (United States)

Shekarabi, Masoud; Girard, Nathalie; Rivière, Jean-Baptiste; Dion, Patrick; Houle, Martin; Toulouse, André; Lafrenière, Ronald G; Vercauteren, Freya; Hince, Pascale; Laganiere, Janet; Rochefort, Daniel; Faivre, Laurence; Samuels, Mark; Rouleau, Guy A

2008-07-01

Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system-specific exon of the with-no-lysine(K)-1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII.

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

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Jean-Sébastien Teoh

2018-01-01

Full Text Available Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently self-repair. This inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to patients. Compared 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 repaired. In particular, several invertebrate species have been shown to rapidly initiate regeneration post-injury, allowing separated axon segments to re-join. This 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 structure. Our recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged neurons. Moreover, 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.

The Central Nervous System and Bone Metabolism: An Evolving Story.

Science.gov (United States)

Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

Structural homeostasis in the nervous system: A balancing act for wiring plasticity and stability

Directory of Open Access Journals (Sweden)

Jun eYin

2015-01-01

Full Text Available Experience-dependent modifications of neural circuits provide the cellular basis for functional adaptation and learning, while presenting significant challenges to the stability of neural networks. The nervous system copes with these perturbations through a variety of compensatory mechanisms with distinct spatial and temporal profiles. Mounting evidence suggests that structural plasticity, through modifications of the number and structure of synapses, or changes in local and long-range connectivity, might contribute to the stabilization of network activity and serve as an important component of the homeostatic regulation of the nervous system. Conceptually similar to the homeostatic regulation of synaptic strength and efficacy, homeostatic structural plasticity has a profound and lasting impact on the intrinsic excitability of the neuron and circuit properties, yet remains largely unexplored. In this review, we examine recent reports describing structural modifications associated with functional compensation in both developing and adult nervous systems, and discuss the potential role for structural homeostasis in maintaining network stability and its implications in physiological and pathological conditions of the nervous systems.

Controlling Underwater Robots with Electronic Nervous Systems

Directory of Open Access Journals (Sweden)

Joseph Ayers

2010-01-01

Full Text Available We are developing robot controllers based on biomimetic design principles. The goal is to realise the adaptive capabilities of the animal models in natural environments. We report feasibility studies of a hybrid architecture that instantiates a command and coordinating level with computed discrete-time map-based (DTM neuronal networks and the central pattern generators with analogue VLSI (Very Large Scale Integration electronic neuron (aVLSI networks. DTM networks are realised using neurons based on a 1-D or 2-D Map with two additional parameters that define silent, spiking and bursting regimes. Electronic neurons (ENs based on Hindmarsh–Rose (HR dynamics can be instantiated in analogue VLSI and exhibit similar behaviour to those based on discrete components. We have constructed locomotor central pattern generators (CPGs with aVLSI networks that can be modulated to select different behaviours on the basis of selective command input. The two technologies can be fused by interfacing the signals from the DTM circuits directly to the aVLSI CPGs. Using DTMs, we have been able to simulate complex sensory fusion for rheotaxic behaviour based on both hydrodynamic and optical flow senses. We will illustrate aspects of controllers for ambulatory biomimetic robots. These studies indicate that it is feasible to fabricate an electronic nervous system controller integrating both aVLSI CPGs and layered DTM exteroceptive reflexes.

CD44: molecular interactions, signalling and functions in the nervous system.

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Grzegorz Marek Wilczynski

2015-05-01

Full Text Available CD44 is the major surface hyaluronan receptor implicated in intercellular and cell-matrix adhesion, cell migration and signalling. It is a transmembrane, highly glycosylated protein with several isoforms resulting from alternative gene splicing. The CD44 molecule consists of several domains serving different functions: the N-terminal extracellular domain, the stem region, the transmembrane domain and the C-terminal tail. In the nervous system, CD44 expression occurs in both glial and neuronal cells. The role of CD44 in the physiology and pathology of the nervous system is not entirely understood, however, there exists evidence suggesting it might be involved in the axon guidance, cytoplasmic Ca2+ clearance, dendritic arborization, synaptic transmission, epileptogenesis, oligodendrocyte and astrocyte differentiation, post-traumatic brain repair and brain tumour development.

Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system.

Science.gov (United States)

Gordon, Tessa; Udina, Esther; Verge, Valerie M K; de Chaves, Elena I Posse

2009-10-01

Injured peripheral but not central nerves regenerate their axons but functional recovery is often poor. We demonstrate that prolonged periods of axon separation from targets and Schwann cell denervation eliminate regenerative capacity in the peripheral nervous system (PNS). A substantial delay of 4 weeks for all regenerating axons to cross a site of repair of sectioned nerve contributes to the long period of separation. Findings that 1h 20Hz bipolar electrical stimulation accelerates axon outgrowth across the repair site and the downstream reinnervation of denervated muscles in rats and human patients, provides a new and exciting method to improve functional recovery after nerve injuries. Drugs that elevate neuronal cAMP and activate PKA promote axon outgrowth in vivo and in vitro, mimicking the electrical stimulation effect. Rapid expression of neurotrophic factors and their receptors and then of growth associated proteins thereafter via cAMP, is the likely mechanism by which electrical stimulation accelerates axon outgrowth from the site of injury in both peripheral and central nervous systems.

The Multifactorial role of Peripheral Nervous System in Bone Growth

Science.gov (United States)

Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

2017-09-01

Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

Mosaic serine proteases in the mammalian central nervous system.

Science.gov (United States)

Mitsui, Shinichi; Watanabe, Yoshihisa; Yamaguchi, Tatsuyuki; Yamaguchi, Nozomi

2008-01-01

We review the structure and function of three kinds of mosaic serine proteases expressed in the mammalian central nervous system (CNS). Mosaic serine proteases have several domains in the proenzyme fragment, which modulate proteolytic function, and a protease domain at the C-terminus. Spinesin/TMPRSS5 is a transmembrane serine protease whose presynaptic distribution on motor neurons in the spinal cord suggests that it is significant for neuronal plasticity. Cell type-specific alternative splicing gives this protease diverse functions by modulating its intracellular localization. Motopsin/PRSS12 is a mosaic protease, and loss of its function causes mental retardation. Recent reports indicate the significance of this protease for cognitive function. We mention the fibrinolytic protease, tissue plasminogen activator (tPA), which has physiological and pathological functions in the CNS.

Peripheral Nervous System Manifestations in Systemic Autoimmune Diseases

OpenAIRE

COJOCARU, Inimioara Mihaela; COJOCARU, Manole; SILOSI, Isabela; VRABIE, Camelia Doina

2014-01-01

The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement ...

Effect of insulin-induced hypoglycaemia on the central nervous system

DEFF Research Database (Denmark)

Jensen, Vivi Flou Hjorth; Bøgh, I. B.; Lykkesfeldt, Jens

2014-01-01

normoglycaemia. Brain glucose concentrations, being approximately 15-20% of the blood glucose concentration in humans, are rigorously maintained during hypoglycaemia through adaptions such as increased cerebral glucose transport, decreased cerebral glucose utilisation and, possibly, by using central nervous...... system glycogen as a glucose reserve. However, during sustained hypoglycaemia, the brain cannot maintain a sufficient glucose influx and, as the cerebral hypoglycaemia becomes severe, electroencephalogram changes, oxidative stress and regional neuronal death ensues. With particular focus on evidence from...

Serotonin-immunoreactivity in the ventral nerve cord of Pycnogonida--support for individually identifiable neurons as ancestral feature of the arthropod nervous system.

Science.gov (United States)

Brenneis, Georg; Scholtz, Gerhard

2015-07-10

The arthropod ventral nerve cord features a comparably low number of serotonin-immunoreactive neurons, occurring in segmentally repeated arrays. In different crustaceans and hexapods, these neurons have been individually identified and even inter-specifically homologized, based on their soma positions and neurite morphologies. Stereotypic sets of serotonin-immunoreactive neurons are also present in myriapods, whereas in the investigated chelicerates segmental neuron clusters with higher and variable cell numbers have been reported. This led to the suggestion that individually identifiable serotonin-immunoreactive neurons are an apomorphic feature of the Mandibulata. To test the validity of this neurophylogenetic hypothesis, we studied serotonin-immunoreactivity in three species of Pycnogonida (sea spiders). This group of marine arthropods is nowadays most plausibly resolved as sister group to all other extant chelicerates, rendering its investigation crucial for a reliable reconstruction of arthropod nervous system evolution. In all three investigated pycnogonids, the ventral walking leg ganglia contain different types of serotonin-immunoreactive neurons, the somata of which occurring mostly singly or in pairs within the ganglionic cortex. Several of these neurons are readily and consistently identifiable due to their stereotypic soma position and characteristic neurite morphology. They can be clearly homologized across different ganglia and different specimens as well as across the three species. Based on these homologous neurons, we reconstruct for their last common ancestor (presumably the pycnogonid stem species) a minimal repertoire of at least seven identified serotonin-immunoreactive neurons per hemiganglion. Beyond that, each studied species features specific pattern variations, which include also some neurons that were not reliably labeled in all specimens. Our results unequivocally demonstrate the presence of individually identifiable serotonin

The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system

Directory of Open Access Journals (Sweden)

Marta Chaverra

2017-05-01

Full Text Available Hereditary sensory and autonomic neuropathies (HSANs are a genetically and clinically diverse group of disorders defined by peripheral nervous system (PNS dysfunction. HSAN type III, known as familial dysautonomia (FD, results from a single base mutation in the gene IKBKAP that encodes a scaffolding unit (ELP1 for a multi-subunit complex known as Elongator. Since mutations in other Elongator subunits (ELP2 to ELP4 are associated with central nervous system (CNS disorders, the goal of this study was to investigate a potential requirement for Ikbkap in the CNS of mice. The sensory and autonomic pathophysiology of FD is fatal, with the majority of patients dying by age 40. While signs and pathology of FD have been noted in the CNS, the clinical and research focus has been on the sensory and autonomic dysfunction, and no genetic model studies have investigated the requirement for Ikbkap in the CNS. Here, we report, using a novel mouse line in which Ikbkap is deleted solely in the nervous system, that not only is Ikbkap widely expressed in the embryonic and adult CNS, but its deletion perturbs both the development of cortical neurons and their survival in adulthood. Primary cilia in embryonic cortical apical progenitors and motile cilia in adult ependymal cells are reduced in number and disorganized. Furthermore, we report that, in the adult CNS, both autonomic and non-autonomic neuronal populations require Ikbkap for survival, including spinal motor and cortical neurons. In addition, the mice developed kyphoscoliosis, an FD hallmark, indicating its neuropathic etiology. Ultimately, these perturbations manifest in a developmental and progressive neurodegenerative condition that includes impairments in learning and memory. Collectively, these data reveal an essential function for Ikbkap that extends beyond the peripheral nervous system to CNS development and function. With the identification of discrete CNS cell types and structures that depend on

Bifurcation of synchronous oscillations into torus in a system of two reciprocally inhibitory silicon neurons: Experimental observation and modeling

International Nuclear Information System (INIS)

Bondarenko, Vladimir E.; Cymbalyuk, Gennady S.; Patel, Girish; DeWeerth, Stephen P.; Calabrese, Ronald L.

2004-01-01

Oscillatory activity in the central nervous system is associated with various functions, like motor control, memory formation, binding, and attention. Quasiperiodic oscillations are rarely discussed in the neurophysiological literature yet they may play a role in the nervous system both during normal function and disease. Here we use a physical system and a model to explore scenarios for how quasiperiodic oscillations might arise in neuronal networks. An oscillatory system of two mutually inhibitory neuronal units is a ubiquitous network module found in nervous systems and is called a half-center oscillator. Previously we created a half-center oscillator of two identical oscillatory silicon (analog Very Large Scale Integration) neurons and developed a mathematical model describing its dynamics. In the mathematical model, we have shown that an in-phase limit cycle becomes unstable through a subcritical torus bifurcation. However, the existence of this torus bifurcation in experimental silicon two-neuron system was not rigorously demonstrated or investigated. Here we demonstrate the torus predicted by the model for the silicon implementation of a half-center oscillator using complex time series analysis, including bifurcation diagrams, mapping techniques, correlation functions, amplitude spectra, and correlation dimensions, and we investigate how the properties of the quasiperiodic oscillations depend on the strengths of coupling between the silicon neurons. The potential advantages and disadvantages of quasiperiodic oscillations (torus) for biological neural systems and artificial neural networks are discussed

Radiation induced effects in the developing central nervous system

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Michelin, S.C.; Perez, M.R. Del

1997-01-01

The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed

A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system.

Science.gov (United States)

Raimondo, Joseph V; Joyce, Bradley; Kay, Louise; Schlagheck, Theresa; Newey, Sarah E; Srinivas, Shankar; Akerman, Colin J

2013-01-01

Within the nervous system, intracellular Cl(-) and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl(-) and pH are often co-regulated, and network activity results in the movement of both Cl(-) and H(+). Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl(-) and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN-a new genetically-encoded ratiometric Cl(-) and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl(-) and H(+) concentrations under a variety of conditions. In addition, we establish the sensor's utility by characterizing activity-dependent ion dynamics in hippocampal neurons.

Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.

Science.gov (United States)

Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A

2013-12-01

Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.

New Insights into c-Ret Signalling Pathway in the Enteric Nervous System and Its Relationship with ALS

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M. J. Luesma

2014-01-01

Full Text Available The receptor tyrosine kinase Ret (c-Ret transduces the glial cell line-derived neurotrophic factor (GDNF signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS. The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.

New insights into c-Ret signalling pathway in the enteric nervous system and its relationship with ALS.

Science.gov (United States)

Luesma, M J; Cantarero, I; Álvarez-Dotu, J M; Santander, S; Junquera, C

2014-01-01

The receptor tyrosine kinase Ret (c-Ret) transduces the glial cell line-derived neurotrophic factor (GDNF) signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS). The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS) during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS) study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.

The nervous system and metabolic dysregulation: emerging evidence converges on ketogenic diet therapy

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David N. Ruskin

2012-03-01

Full Text Available A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high-fat, low-carbohydrate ketogenic diet debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, ketogenic diet therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. More recently, cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders - although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a ketogenic diet and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a ketogenic diet on cognition and recent data on the effects of a ketogenic diet on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system.

The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy

Science.gov (United States)

Ruskin, David N.; Masino, Susan A.

2012-01-01

A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high fat, low-carbohydrate ketogenic diet (KD) debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, KD therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. Cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders – although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a KD and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a KD on cognition and recent data on the effects of a KD on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system. PMID:22470316

Nervous system development in the Pacific oyster, Crassostrea gigas (Mollusca: Bivalvia).

Science.gov (United States)

Yurchenko, Olga V; Skiteva, Olga I; Voronezhskaya, Elena E; Dyachuk, Vyacheslav A

2018-01-01

Bivalves comprise a large, highly diverse taxon of invertebrate species. Developmental studies of neurogenesis among species of Bivalvia are limited. Due to a lack of neurogenesis information, it is difficult to infer a ground pattern for Bivalvia. To provide more comprehensive morphogenetic data on bivalve molluscs and relationships among molluscan clades, we investigated neurogenesis in the Pacific oyster, Crassostrea gigas , from the appearance of the first sensory cells to the formation of the larval ganglionic nervous system by co-immunocytochemistry of the neuronal markers FMRFamide or 5-HT and vesicular acetylcholine transporter (VAChT). Neurogenesis begins with the emergence of the apical serotonin-immunoreactive (5-HT-ir) sensory cells and paired sensory posttrochal dorsal and ventral FMRFamide-immunoreactive (FMRFamide-ir) cells at the early trochophore stage. Later, at the early veliger stage, the apical organ (AO) includes 5-HT-ir, FMRFamide-ir, and VAChT-ir cells. At the same stage, VAChT-ir cells appear in the posterior region of larvae and send axons towards the AO. Thus, FMRFamide-ir neurites and VAChT-ir processes form scaffolds for longitudinal neurite bundles develop into the paired ventral nerve cords (VNC). Later-appearing axons from the AO/CG neurons join the neurite bundles comprising the VNC. All larval ganglia appear along the VNC as paired or fused (epiathroid) clusters in late veliger and pediveliger larvae. We observed the transformation of the AO into the cerebral ganglia, which abundantly innervated the velum, and the transformation of ventral neurons into the pedal ganglia, innervating the foot, gills, and anterior adductor muscle. The visceral ganglia appear last in the pediveliger oyster and innervate the visceral mass and posterior adductor of premetamorphic larvae. In addition, a local FMRFamide-ir network was detected in the digestive system of pediveliger larvae. We identified VAChT-ir nervous elements in oyster larvae, which

Peripheral nervous system involvement in chronic spinal cord injury

DEFF Research Database (Denmark)

Tankisi, Hatice; Pugdahl, Kirsten; Rasmussen, Mikkel Mylius

2015-01-01

Introduction: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Methods: Twelve subjects with chronic low cervical or thoracic SCI were included......), and the amount of SA correlated inversely with reflex activity and nerve length. Fibular nerve entrapment across the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1. Apart from entrapment neuropathies, NCS changes were found predominantly in motor nerves. Conclusion: The presence...

Region-specific vulnerability to lipid peroxidation and evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the healthy adult human central nervous system.

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Naudí, Alba; Cabré, Rosanna; Dominguez-Gonzalez, Mayelin; Ayala, Victoria; Jové, Mariona; Mota-Martorell, Natalia; Piñol-Ripoll, Gerard; Gil-Villar, Maria Pilar; Rué, Montserrat; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2017-05-01

Lipids played a determinant role in the evolution of the brain. It is postulated that the morphological and functional diversity among neural cells of the human central nervous system (CNS) is projected and achieved through the expression of particular lipid profiles. The present study was designed to evaluate the differential vulnerability to oxidative stress mediated by lipids through a cross-regional comparative approach. To this end, we compared 12 different regions of CNS of healthy adult subjects, and the fatty acid profile and vulnerability to lipid peroxidation, were determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), respectively. In addition, different components involved in PUFA biosynthesis, as well as adaptive defense mechanisms against lipid peroxidation, were also measured by western blot and immunohistochemistry, respectively. We found that: i) four fatty acids (18.1n-9, 22:6n-3, 20:1n-9, and 18:0) are significant discriminators among CNS regions; ii) these differential fatty acid profiles generate a differential selective neural vulnerability (expressed by the peroxidizability index); iii) the cross-regional differences for the fatty acid profiles follow a caudal-cranial gradient which is directly related to changes in the biosynthesis pathways which can be ascribed to neuronal cells; and iv) the higher the peroxidizability index for a given human brain region, the lower concentration of the protein damage markers, likely supported by the presence of adaptive antioxidant mechanisms. In conclusion, our results suggest that there is a region-specific vulnerability to lipid peroxidation and offer evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the human central nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Myelin injury in the central nervous system and Alzheimer's diseases.

Science.gov (United States)

Wang, Sha-Sha; Zhang, Zhao; Zhu, Tian-Bi; Chu, Shi-Feng; He, Wen-Bin; Chen, Nai-Hong

2018-05-03

Myelin is a membrane wrapped around the axon of the nerve cell, which is composed of the mature oligodendrocytes. The role of myelin is to insulate and prevent the nerve electrical impulses from the axon of the neurons to the axons of the other neurons, which is essential for the proper functioning of the nervous system. Minor changes in myelin thickness could lead to substantial changes in conduction speed and may thus alter neural circuit function. Demyelination is the myelin damage, which characterized by the loss of nerve sheath and the relative fatigue of the neuronal sheath and axon. Studies have shown that myelin injury may be closely related to neurodegenerative diseases and may be an early diagnostic criteria and therapeutic target. Thus this review summarizes the recent result of pathologic effect and signal pathways of myelin injury in neurodegenerative diseases, especially the Alzheimer's disease to provide new and effective therapeutic targets. Copyright © 2018. Published by Elsevier Inc.

Timing of neuron development in the rodent vestibular system

Science.gov (United States)

Keefe, J. R.

1982-01-01

The timing of cell generation (onset and duration) in the developing rat vestibular and proprioceptive systems is investigated. The results clearly indicate a defined time-span for generation of all neurons in the central nervous system nuclei studied. This cytogenetic period in both vestibular and proprioceptive sensory nuclei is determined to occur during and immediately after placentation, a potentially critical period for spaceflight exposure due to alterations in maternal physiology.

A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system

Science.gov (United States)

Raimondo, Joseph V.; Joyce, Bradley; Kay, Louise; Schlagheck, Theresa; Newey, Sarah E.; Srinivas, Shankar; Akerman, Colin J.

2013-01-01

Within the nervous system, intracellular Cl− and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl− and pH are often co-regulated, and network activity results in the movement of both Cl− and H+. Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl− and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN—a new genetically-encoded ratiometric Cl− and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl− and H+ concentrations under a variety of conditions. In addition, we establish the sensor's utility by characterizing activity-dependent ion dynamics in hippocampal neurons. PMID:24312004

A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system

Directory of Open Access Journals (Sweden)

Joseph Valentino Raimondo

2013-11-01

Full Text Available Within the nervous system, intracellular Cl- and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission and network excitability. Cl- and pH are often co-regulated, and network activity results in the movement of both Cl- and H+. Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl- and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN - a new genetically-encoded ratiometric Cl- and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl- and H+ concentrations under a variety of conditions. In addition, we establish the sensor’s utility by characterizing activity-dependent ion dynamics in hippocampal neurons.

Dynamic systems approaches and levels of analysis in the nervous system

Science.gov (United States)

Parker, David; Srivastava, Vipin

2013-01-01

Various analyses are applied to physiological signals. While epistemological diversity is necessary to address effects at different levels, there is often a sense of competition between analyses rather than integration. This is evidenced by the differences in the criteria needed to claim understanding in different approaches. In the nervous system, neuronal analyses that attempt to explain network outputs in cellular and synaptic terms are rightly criticized as being insufficient to explain global effects, emergent or otherwise, while higher-level statistical and mathematical analyses can provide quantitative descriptions of outputs but can only hypothesize on their underlying mechanisms. The major gap in neuroscience is arguably our inability to translate what should be seen as complementary effects between levels. We thus ultimately need approaches that allow us to bridge between different spatial and temporal levels. Analytical approaches derived from critical phenomena in the physical sciences are increasingly being applied to physiological systems, including the nervous system, and claim to provide novel insight into physiological mechanisms and opportunities for their control. Analyses of criticality have suggested several important insights that should be considered in cellular analyses. However, there is a mismatch between lower-level neurophysiological approaches and statistical phenomenological analyses that assume that lower-level effects can be abstracted away, which means that these effects are unknown or inaccessible to experimentalists. As a result experimental designs often generate data that is insufficient for analyses of criticality. This review considers the relevance of insights from analyses of criticality to neuronal network analyses, and highlights that to move the analyses forward and close the gap between the theoretical and neurobiological levels, it is necessary to consider that effects at each level are complementary rather than in

Enteric neurons show a primary cilium.

Science.gov (United States)

Luesma, Ma José; Cantarero, Irene; Castiella, Tomás; Soriano, Mario; Garcia-Verdugo, José Manuel; Junquera, Concepción

2013-01-01

The primary cilium is a non-motile cilium whose structure is 9+0. It is involved in co-ordinating cellular signal transduction pathways, developmental processes and tissue homeostasis. Defects in the structure or function of the primary cilium underlie numerous human diseases, collectively termed ciliopathies. The presence of single cilia in the central nervous system (CNS) is well documented, including some choroid plexus cells, neural stem cells, neurons and astrocytes, but the presence of primary cilia in differentiated neurons of the enteric nervous system (ENS) has not yet been described in mammals to the best of our knowledge. The enteric nervous system closely resembles the central nervous system. In fact, the ultrastructure of the ENS is more similar to the CNS ultrastructure than to the rest of the peripheral nervous system. This research work describes for the first time the ultrastructural characteristics of the single cilium in neurons of rat duodenum myenteric plexus, and reviews the cilium function in the CNS to propose the possible role of cilia in the ENS cells. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Central- and autonomic nervous system coupling in schizophrenia

Science.gov (United States)

Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

2016-01-01

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

What Are the Parts of the Nervous System?

Science.gov (United States)

... Email Print What are the parts of the nervous system? The nervous system consists of two main parts: the central nervous system and the peripheral nervous system: The central nervous system is made up of the brain and ...

Visualization of Sensory Neurons and Their Projections in an Upper Motor Neuron Reporter Line.

Science.gov (United States)

Genç, Barış; Lagrimas, Amiko Krisa Bunag; Kuru, Pınar; Hess, Robert; Tu, Michael William; Menichella, Daniela Maria; Miller, Richard J; Paller, Amy S; Özdinler, P Hande

2015-01-01

Visualization of peripheral nervous system axons and cell bodies is important to understand their development, target recognition, and integration into complex circuitries. Numerous studies have used protein gene product (PGP) 9.5 [a.k.a. ubiquitin carboxy-terminal hydrolase L1 (UCHL1)] expression as a marker to label sensory neurons and their axons. Enhanced green fluorescent protein (eGFP) expression, under the control of UCHL1 promoter, is stable and long lasting in the UCHL1-eGFP reporter line. In addition to the genetic labeling of corticospinal motor neurons in the motor cortex and degeneration-resistant spinal motor neurons in the spinal cord, here we report that neurons of the peripheral nervous system are also fluorescently labeled in the UCHL1-eGFP reporter line. eGFP expression is turned on at embryonic ages and lasts through adulthood, allowing detailed studies of cell bodies, axons and target innervation patterns of all sensory neurons in vivo. In addition, visualization of both the sensory and the motor neurons in the same animal offers many advantages. In this report, we used UCHL1-eGFP reporter line in two different disease paradigms: diabetes and motor neuron disease. eGFP expression in sensory axons helped determine changes in epidermal nerve fiber density in a high-fat diet induced diabetes model. Our findings corroborate previous studies, and suggest that more than five months is required for significant skin denervation. Crossing UCHL1-eGFP with hSOD1G93A mice generated hSOD1G93A-UeGFP reporter line of amyotrophic lateral sclerosis, and revealed sensory nervous system defects, especially towards disease end-stage. Our studies not only emphasize the complexity of the disease in ALS, but also reveal that UCHL1-eGFP reporter line would be a valuable tool to visualize and study various aspects of sensory nervous system development and degeneration in the context of numerous diseases.

Reciprocal regulation of A-to-I RNA editing and the vertebrate nervous system

Directory of Open Access Journals (Sweden)

Andrew Charles Penn

2013-04-01

Full Text Available The fine control of molecules mediating communication in the nervous system is key to adjusting neuronal responsiveness during development and in maintaining the stability of established networks in the face of altered sensory input. To prevent culmination of pathological recurrent network excitation or debilitating periods of quiescence, adaptive alterations occur in the signalling molecules and ion channels that control membrane excitability and synaptic transmission. However, rather than encoding (and thus ‘hardwiring’ modified gene copies, the nervous systems of metazoa have opted for expanding on post-transcriptional pre-mRNA splicing by altering key encoded amino acids using a conserved mechanism of A-to-I RNA editing: the enzymatic deamination of adenosine resulting in a change in the nucleotide to inosine. Inosine exhibits similar base-pairing properties to guanosine with respect to tRNA codon recognition, replication by polymerases and RNA secondary structure forming capacity. In addition to recoding within the open reading frame, adenosine deamination also occurs with high frequency throughout the non-coding transcriptome, where it affects multiple aspects of RNA metabolism and gene expression. We will describe here the recoding function of key RNA editing targets in the mammalian central nervous system (CNS and their potential to be regulated. We will then discuss how interactions of A-to-I editing with gene expression and alternative splicing could play a wider role in regulating the neuronal transcriptome. Finally, we will highlight the increasing complexity of this multifaceted control hub by summarising new findings from high-throughput studies.

Firing dynamics of an autaptic neuron

International Nuclear Information System (INIS)

Wang Heng-Tong; Chen Yong

2015-01-01

Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh–Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. (topical review)

Left-right asymmetries of behaviour and nervous system in invertebrates.

Science.gov (United States)

Frasnelli, Elisa; Vallortigara, Giorgio; Rogers, Lesley J

2012-04-01

Evidence of left-right asymmetries in invertebrates has begun to emerge, suggesting that lateralization of the nervous system may be a feature of simpler brains as well as more complex ones. A variety of studies have revealed sensory and motor asymmetries in behaviour, as well as asymmetries in the nervous system, in invertebrates. Asymmetries in behaviour are apparent in olfaction (antennal asymmetries) and in vision (preferential use of the left or right visual hemifield during activities such as foraging or escape from predators) in animals as different as bees, fruitflies, cockroaches, octopuses, locusts, ants, spiders, crabs, snails, water bugs and cuttlefish. Asymmetries of the nervous system include lateralized position of specific brain structures (e.g., in fruitflies and snails) and of specific neurons (e.g., in nematodes). As in vertebrates, lateralization can occur both at the individual and at the population-level in invertebrates. Theoretical models have been developed supporting the hypothesis that the alignment of the direction of behavioural and brain asymmetries at the population-level could have arisen as a result of social selective pressures, when individually asymmetrical organisms had to coordinate with each other. The evidence reviewed suggests that lateralization at the population-level may be more likely to occur in social species among invertebrates, as well as vertebrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neuromorphic neural interfaces: from neurophysiological inspiration to biohybrid coupling with nervous systems

Science.gov (United States)

Broccard, Frédéric D.; Joshi, Siddharth; Wang, Jun; Cauwenberghs, Gert

2017-08-01

Objective. Computation in nervous systems operates with different computational primitives, and on different hardware, than traditional digital computation and is thus subjected to different constraints from its digital counterpart regarding the use of physical resources such as time, space and energy. In an effort to better understand neural computation on a physical medium with similar spatiotemporal and energetic constraints, the field of neuromorphic engineering aims to design and implement electronic systems that emulate in very large-scale integration (VLSI) hardware the organization and functions of neural systems at multiple levels of biological organization, from individual neurons up to large circuits and networks. Mixed analog/digital neuromorphic VLSI systems are compact, consume little power and operate in real time independently of the size and complexity of the model. Approach. This article highlights the current efforts to interface neuromorphic systems with neural systems at multiple levels of biological organization, from the synaptic to the system level, and discusses the prospects for future biohybrid systems with neuromorphic circuits of greater complexity. Main results. Single silicon neurons have been interfaced successfully with invertebrate and vertebrate neural networks. This approach allowed the investigation of neural properties that are inaccessible with traditional techniques while providing a realistic biological context not achievable with traditional numerical modeling methods. At the network level, populations of neurons are envisioned to communicate bidirectionally with neuromorphic processors of hundreds or thousands of silicon neurons. Recent work on brain-machine interfaces suggests that this is feasible with current neuromorphic technology. Significance. Biohybrid interfaces between biological neurons and VLSI neuromorphic systems of varying complexity have started to emerge in the literature. Primarily intended as a

Radioautography of the central nervous system and pituitary after 3H steroid hormones injection into different mammals

International Nuclear Information System (INIS)

Warembourg, M.

1977-01-01

The central nervous system and pituitary of various mammals were examined by radioautography after injection of different tritiated steroid hormones. After injection of 3 H estradiol into ovariectomized mice, radioautograms revealed a significant labelling in cells of the amygdala, the bed nucleus of the stria terminalis, the nucleus preopticus medialis, the nuclei arcuatus and ventro-medialis. After injection of 3 H testosterone into castrated rats, the central nervous system and the anterior pituitary contained labelled cells. In the hypothalamus, the distribution pattern of androgen-neurons appears to be similar from the estrogen-neuron areas. After injection of 3 H progesterone into castrated estrogen-primed guinea-pigs, labelled neurons have been in the regions of nucleus arcuatus and nucleus preopticus suprachiasmaticus. After injection of 3 H corticosterone into adrenalectomized male rats, radioactivity was found to be selectively concentrated in neurons of septum, hippocampal complex indusium griseum, amygdala and in certain areas of the cortex. Most of the silver grains were localized in the nuclei of labelled cells. On the other hand, after injection of 3 H dexamethasone radioactivity concentration was high in the medial basal hypothalamus, in the anterior pituitary and in the pineal gland. Differences appear to exist in the topographic distribution of dexamethasone and corticosterone-concentrating cells [fr

Larval nervous systems

DEFF Research Database (Denmark)

Nielsen, Claus

2015-01-01

as the adult central nervous system (CNS). Two structures can be recognized, viz. a pair of cerebral ganglia, which form the major part of the adult brain, and a blastoporal (circumblastoporal) nerve cord, which becomes differentiated into a perioral loop, paired or secondarily fused ventral nerve cords......, and the nervous systems of echinoderms and enteropneusts appear completely enigmatic. The ontogeny of the chordate CNS can perhaps be interpreted as a variation of the ontogeny of the blastoporal nerve cord of the protostomes, and this is strongly supported by patterns of gene expression. The presence...

[Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

Science.gov (United States)

Zając-Spychała, Olga; Wachowiak, Jacek

2012-01-01

Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in

Location and function of serotonin in the central and peripheral nervous system of the Colorado potato beetle

NARCIS (Netherlands)

Haeften, van T.

1993-01-01

In this thesis we have localized serotoninergic neurons in the central and peripheral nervous system of the Colorado potato beetle, Leptinotarsa decemlineata by means of immunohistochemistry with a specific antiserurn to serotonin and assessed the possible role of these

The central nervous system

International Nuclear Information System (INIS)

Holmes, R.A.

1984-01-01

The first section presents a comprehensive evaluation of radionuclide imaging of the central nervous system and provides a comparison of the detection accuracies of radionuclide imaging (RNI) and XCT in certain lesions, realizing that the XCT results may vary when radiocontrast or newer generation XCT scanners are used. Although conventional radionuclide imaging of the central nervous system has experienced no significant changes over the last 7 years except for mild refinements, a new section has been added on positron emission tomography (PET). Most positron radiopharmaceuticals passively cross the intact blood-brain barrier, and their localization has catalyzed renewed interest in our ability to metabolically study and obtain images of the central nervous system. The section on radionuclide cisternography has been rewritten to reflect present day practice and the wider application of XCT in describing conditions affecting the ventricular system

Glucagon-like Peptide-1 and the Central/Peripheral Nervous System

DEFF Research Database (Denmark)

Muscogiuri, Giovanna; DeFronzo, Ralph A; Gastaldelli, Amalia

2017-01-01

Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary trac...... human trials report a neuroprotective effect of GLP-1-RAs in Alzheimer's and Parkinson's disease. In this review, we discuss the role of GLP-1 and GLP-1-RAs in the nervous system with focus on GLP-1 actions on appetite regulation, glucose homeostasis, and neuroprotection....

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

NARCIS (Netherlands)

Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

2015-01-01

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely

Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases.

Science.gov (United States)

Radu, Beatrice Mihaela; Banciu, Adela; Banciu, Daniel Dumitru; Radu, Mihai

2016-01-01

Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed. © 2016 Elsevier Inc. All rights reserved.

A High Density Electrophysiological Data Analysis System for a Peripheral Nerve Interface Communicating with Individual Neurons in the Brain

Science.gov (United States)

2016-11-14

of-the-art instrumentation to communicate with individual neurons in the brain and the peripheral nervous system. The major theme of the research is...Nerve Interface Communicating with Individual Neurons in the Brain The views, opinions and/or findings contained in this report are those of the author... Communicating with Individual Neurons in the Brain Report Title The high density electrophysiological data acquisition system obtained through this

In Vitro Reconstruction of Neuronal Networks Derived from Human iPS Cells Using Microfabricated Devices.

Directory of Open Access Journals (Sweden)

Yuzo Takayama

Full Text Available Morphology and function of the nervous system is maintained via well-coordinated processes both in central and peripheral nervous tissues, which govern the homeostasis of organs/tissues. Impairments of the nervous system induce neuronal disorders such as peripheral neuropathy or cardiac arrhythmia. Although further investigation is warranted to reveal the molecular mechanisms of progression in such diseases, appropriate model systems mimicking the patient-specific communication between neurons and organs are not established yet. In this study, we reconstructed the neuronal network in vitro either between neurons of the human induced pluripotent stem (iPS cell derived peripheral nervous system (PNS and central nervous system (CNS, or between PNS neurons and cardiac cells in a morphologically and functionally compartmentalized manner. Networks were constructed in photolithographically microfabricated devices with two culture compartments connected by 20 microtunnels. We confirmed that PNS and CNS neurons connected via synapses and formed a network. Additionally, calcium-imaging experiments showed that the bundles originating from the PNS neurons were functionally active and responded reproducibly to external stimuli. Next, we confirmed that CNS neurons showed an increase in calcium activity during electrical stimulation of networked bundles from PNS neurons in order to demonstrate the formation of functional cell-cell interactions. We also confirmed the formation of synapses between PNS neurons and mature cardiac cells. These results indicate that compartmentalized culture devices are promising tools for reconstructing network-wide connections between PNS neurons and various organs, and might help to understand patient-specific molecular and functional mechanisms under normal and pathological conditions.

Phenotypic expression in the developing murine enteric nervous system

International Nuclear Information System (INIS)

Rothman, T.P.; Gershon, M.D.

1982-01-01

The development of the enteric nervous system was examined in fetal mice. Synthesis of [3H] acetylcholine ([3H]ACh) from [3H]choline and acetylcholinesterase histochemistry were used as phenotypic markers for cholinergic neurons, while the radioautographic detection of the specific uptake of [3H]serotonin (5-[3H]HT) and immunocytochemical staining with antiserum to 5-HT marked serotonergic neurons. The gut also was examined by light and electron microscopy. Development of the gut was studied in situ and in explants grown in organotypic tissue culture. Neurons were first detected morphologically in the foregut on embryonic day 12 (E12). Synthesis of [3H]ACh was detectable on days E10 to E12 but increased markedly between days E13 and E14. Uptake and radioautographic labeling by 5-[3H]HT was seen first in the foregut on day E12, in the colon on day E13, and in the terminal colon on day E14. Gut explanted from both distal and proximal bowel prior to the time when neurons could be detected (days E9 to E11) nevertheless formed neurons in culture. These cultures of early explants displayed markers for both cholinergic and serotonergic neurons. Enhances development of both cholinergic and serotonergic neurons was found in cultures explanted at day E11 over that found in cultures explanted on days E9 or E10. The evidence presented indicates (1) that enteric neurons develop from nonrecognizable precursors, (2) that the proximodistal gradient in neuronal phenotypic expression probably is not related to a proximodistal migration of precursor cells down the gut, (3) that the colonization of the bowel by neuronal precursors may be a prolonged process continuing from day E9 at least through day E11, (4) that the first pool of neuronal primordia to colonize the developing bowel can produce both cholinergic and serotonergic neurons

Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment and dysfunction in central nervous system: the potential roles played by microglia

Directory of Open Access Journals (Sweden)

Yang Q

2013-08-01

Full Text Available Qingchan Yang,1,* Yan Wang,2,* Jing Feng,2 Jie Cao,2 Baoyuan Chen2 1Graduate School of Tianjin Medical University, 2Respiratory Department, Tianjin Medical University General Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Abstract: Obstructive sleep apnea (OSA is a common condition characterized by repetitive episodes of complete (apnea or partial (hypopnea obstruction of the upper airway during sleep, resulting in oxygen desaturation and arousal from sleep. Intermittent hypoxia (IH resulting from OSA may cause structural neuron damage and dysfunction in the central nervous system (CNS. Clinically, it manifests as neurocognitive and behavioral deficits with oxidative stress and inflammatory impairment as its pathophysiological basis, which are mediated by microglia at the cellular level. Microglia are dominant proinflammatory cells in the CNS. They induce CNS oxidative stress and inflammation, mainly through mitochondria, reduced nicotinamide adenine dinucleotide phosphate oxidase, and the release of excitatory toxic neurotransmitters. The balance between neurotoxic versus protective and anti- versus proinflammatory microglial factors might determine the final roles of microglia after IH exposure from OSA. Microglia inflammatory impairments will continue and cascade persistently upon activation, ultimately resulting in clinically significant neuron damage and dysfunction in the CNS. In this review article, we summarize the mechanisms of structural neuron damage in the CNS and its concomitant dysfunction due to IH from OSA, and the potential roles played by microglia in this process. Keywords: intermittent hypoxia, obstructive sleep apnea, microglia, inflammation, apoptosis

Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

Science.gov (United States)

Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

1997-01-01

The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

Science.gov (United States)

Hawro, T; Bogucki, A; Krupińska-Kun, M; Maurer, M; Woźniacka, A

2015-12-01

Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE. © The Author(s) 2015.

Applications of CRISPR/Cas9 in the Mammalian Central Nervous System.

Science.gov (United States)

Savell, Katherine E; Day, Jeremy J

2017-12-01

Within the central nervous system, gene regulatory mechanisms are crucial regulators of cellular development and function, and dysregulation of these systems is commonly observed in major neuropsychiatric and neurological disorders. However, due to a lack of tools to specifically modulate the genome and epigenome in the central nervous system, many molecular and genetic mechanisms underlying cognitive function and behavior are still unknown. Although genome editing tools have been around for decades, the recent emergence of inexpensive, straightforward, and widely accessible CRISPR/Cas9 systems has led to a revolution in gene editing. The development of the catalytically dead Cas9 (dCas9) expanded this flexibility even further by acting as an anchoring system for fused effector proteins, structural scaffolds, and RNAs. Together, these advances have enabled robust, modular approaches for specific targeting and modification of the local chromatin environment at a single gene. This review highlights these advancements and how the combination of powerful modulatory tools paired with the versatility of CRISPR-Cas9-based systems offer great potential for understanding the underlying genetic and epigenetic contributions of neuronal function, behavior, and neurobiological diseases.

Are astrocytes executive cells within the central nervous system?

Directory of Open Access Journals (Sweden)

Roberto E. Sica

2016-08-01

Full Text Available ABSTRACT Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson’s disease, Alzheimer’s dementia, Huntington’s dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.

Functions of flavonoids in the central nervous system: Astrocytes as targets for natural compounds.

Science.gov (United States)

Matias, Isadora; Buosi, Andrea Schmidt; Gomes, Flávia Carvalho Alcantara

2016-05-01

In the last decade, there have been major advances in the understanding of the role of glial cells as key elements in the formation, maintenance and refinement of synapses. Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives on the restoration of the injured brain. Among these compounds, flavonoids stand out as molecules easily obtainable in the diet that have remarkable effects on cognitive performance and behavior. Nevertheless, little is known about the cellular and molecular mechanisms underlying the actions of flavonoids in the nervous system. The present review presents recent advances in the effects of natural compounds, particularly flavonoids, in the nervous system. We shed light on astrocytes as targets of flavonoids and discuss how this interaction might contribute to the effects of flavonoids on neuronal survival, differentiation and function. Finally, we discuss how the effects of flavonoids on astrocytes might contribute to the development of alternative therapeutic approaches to the treatment of neural diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

microRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases

DEFF Research Database (Denmark)

Christensen, Mette; Schratt, Gerhard M

2009-01-01

microRNAs, small non-coding RNAs that regulate gene expression at the post-transcriptional level, are emerging as important regulatory molecules involved in the fine-tuning of gene expression during neuronal development and function. microRNAs have roles during neuronal stem cell commitment...... and early differentiation as well as in later stages of neuronal development, such as dendritogenesis and synaptic plasticity. A link between microRNAs and neurological diseases, such as neurodegeneration or synaptic dysfunction, is becoming increasingly clear. This review summarizes the current knowledge...... of the function of microRNAs in the developing and adult nervous system and their potential contribution to the etiology of neurological diseases....

The soft mechanical signature of glial scars in the central nervous system

Science.gov (United States)

Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

2017-03-01

Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

Do enteric neurons make hypocretin? ☆

Science.gov (United States)

Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

2008-01-01

Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin. PMID:18191238

A map of octopaminergic neurons in the Drosophila brain.

Science.gov (United States)

Busch, Sebastian; Selcho, Mareike; Ito, Kei; Tanimoto, Hiromu

2009-04-20

The biogenic amine octopamine modulates diverse behaviors in invertebrates. At the single neuron level, the mode of action is well understood in the peripheral nervous system owing to its simple structure and accessibility. For elucidating the role of individual octopaminergic neurons in the modulation of complex behaviors, a detailed analysis of the connectivity in the central nervous system is required. Here we present a comprehensive anatomical map of candidate octopaminergic neurons in the adult Drosophila brain: including the supra- and subesophageal ganglia. Application of the Flp-out technique enabled visualization of 27 types of individual octopaminergic neurons. Based on their morphology and distribution of genetic markers, we found that most octopaminergic neurons project to multiple brain structures with a clear separation of dendritic and presynaptic regions. Whereas their major dendrites are confined to specific brain regions, each cell type targets different, yet defined, neuropils distributed throughout the central nervous system. This would allow them to constitute combinatorial modules assigned to the modulation of distinct neuronal processes. The map may provide an anatomical framework for the functional constitution of the octopaminergic system. It also serves as a model for the single-cell organization of a particular neurotransmitter in the brain. 2009 Wiley-Liss, Inc.

Smart electromechanical systems the central nervous system

CERN Document Server

Kurbanov, Vugar

2017-01-01

This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

Quantitative autoradiographic characterization of GA-BAB receptors in mammalian central nervous system

International Nuclear Information System (INIS)

Chu, D.Chin-Mei.

1989-01-01

The inhibitory effects of the amino acid neurotransmitter γ-aminobutyric acid (GABA) within the nervous system appear to be mediated through two distinct classes of receptors: GABA A and GABA B receptors. A quantitative autoradiographic method with 3 H-GABA was developed to examine the hypotheses that GABA A and GABA B sites have distinct anatomical distributions, pharmacologic properties, and synaptic localizations within the rodent nervous system. The method was also applied to a comparative study of these receptors in postmortem human brain from individuals afflicted with Alzheimer's disease and those without neurologic disease. The results indicated that GABA B receptors occur in fewer numbers and have a lower affinity for GABA than GABA A receptors in both rodent and human brain. Within rodent brain, the distribution of these two receptor populations were clearly distinct. GABA B receptors were enriched in the medial habenula, interpeduncular nucleus, cerebellar molecular layer and olfactory glomerular layer. After selective lesions of postsynaptic neurons of the corticostriatal and perforant pathway, both GABA B and GABA A receptors were significantly decreased in number. Lesions of the presynaptic limbs of the perforant but not the corticostriatal pathway resulted in upregulation of both GABA receptors in the area of innervation. GABA B receptors were also upregulated in CA3 dendritic regions after destruction of dentate granule neurons

Nervous system examination on YouTube

OpenAIRE

Azer Samy A; AlEshaiwi Sarah M; AlGrain Hala A; AlKhelaif Rana A

2012-01-01

Abstract Background Web 2.0 sites such as YouTube have become a useful resource for knowledge and are used by medical students as a learning resource. This study aimed at assessing videos covering the nervous system examination on YouTube. Methods A research of YouTube was conducted from 2 November to 2 December 2011 using the following key words “nervous system examination”, “nervous system clinical examination”, “cranial nerves examination”, “CNS examination”, “examination of cerebellum”, “...

The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis.

Science.gov (United States)

Huang, Yung-An; Kao, Chun-Wei; Liu, Kuang-Kai; Huang, Hou-Syun; Chiang, Ming-Han; Soo, Ching-Ren; Chang, Huan-Cheng; Chiu, Tzai-Wen; Chao, Jui-I; Hwang, Eric

2014-11-05

Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration).

The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis

Science.gov (United States)

Huang, Yung-An; Kao, Chun-Wei; Liu, Kuang-Kai; Huang, Hou-Syun; Chiang, Ming-Han; Soo, Ching-Ren; Chang, Huan-Cheng; Chiu, Tzai-Wen; Chao, Jui-I.; Hwang, Eric

2014-11-01

Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration).

Systemic Glucoregulation by Glucose-Sensing Neurons in the Ventromedial Hypothalamic Nucleus (VMH).

Science.gov (United States)

Shimazu, Takashi; Minokoshi, Yasuhiko

2017-05-01

The ventromedial hypothalamic nucleus (VMH) regulates glucose production in the liver as well as glucose uptake and utilization in peripheral tissues, including skeletal muscle and brown adipose tissue, via efferent sympathetic innervation and neuroendocrine mechanisms. The action of leptin on VMH neurons also increases glucose uptake in specific peripheral tissues through the sympathetic nervous system, with improved insulin sensitivity. On the other hand, subsets of VMH neurons, such as those that express steroidogenic factor 1 (SF1), sense changes in the ambient glucose concentration and are characterized as glucose-excited (GE) and glucose-inhibited (GI) neurons whose action potential frequency increases and decreases, respectively, as glucose levels rise. However, how these glucose-sensing (GE and GI) neurons in the VMH contribute to systemic glucoregulation remains poorly understood. In this review, we provide historical background and discuss recent advances related to glucoregulation by VMH neurons. In particular, the article describes the role of GE neurons in the control of peripheral glucose utilization and insulin sensitivity, which depend on mitochondrial uncoupling protein 2 of the neurons, as well as that of GI neurons in the control of hepatic glucose production through hypoglycemia-induced counterregulatory mechanisms.

Model System for Live Imaging of Neuronal Responses to Injury and Repair

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Mathieu Gravel

2011-11-01

Full Text Available Although it has been well established that induction of growth-associated protein-43 (GAP-43 during development coincides with axonal outgrowth and early synapse formation, the existence of neuronal plasticity and neurite outgrowth in the adult central nervous system after injuries is more controversial. To visualize the processes of neuronal injury and repair in living animals, we generated reporter mice for bioluminescence and fluorescence imaging bearing the luc (luciferase and gfp (green fluorescent protein reporter genes under the control of the murine GAP-43 promoter. Reporter functionality was first observed during the development of transgenic embryos. Using in vivo bioluminescence and fluorescence imaging, we visualized induction of the GAP-43 signals from live embryos starting at E10.5, as well as neuronal responses to brain and peripheral nerve injuries (the signals peaked at 14 days postinjury. Moreover, three-dimensional analysis of the GAP-43 bioluminescent signal confirmed that it originated from brain structures affected by ischemic injury. The analysis of fluorescence signal at cellular level revealed colocalization between endogenous protein and the GAP-43-driven gfp transgene. Taken together, our results suggest that the GAP-43-luc/gfp reporter mouse represents a valid model system for real-time analysis of neurite outgrowth and the capacity of the adult nervous system to regenerate after injuries.

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

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Gombash, S E; Cowley, C J; Fitzgerald, J A; Lepak, C A; Neides, M G; Hook, K; Todd, L J; Wang, G-D; Mueller, C; Kaspar, B K; Bielefeld, E C; Fischer, A J; Wood, J D; Foust, K D

2017-10-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

[Two-nuclear neurons: sincitial fusion or amitotic division].

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Sotnikov, O S; Frumkina, L E; Lactionova, A A; Paramonova, N M; Novakovskaia, S A

2011-01-01

In the review the history of research two-nuclear neurons is stated and two hypotheses about mechanisms of their formation are analysed: by sincitial fusion or amytotic divisions. The facts of discrepancy of the former orthodox cellular theory categorically denying possibility sincitial of communications in nervous system and of sincitial fusion neurons are mentioned. As an example results of ultrastructural researches of occurrence sincitium in a cortex of the big brain of rats, in autonomic ganglions, in hypocampus and a cerebellum of adult animals are presented. The video data of the sincitial fusion of live neurons and the mechanism of formation multinuclear neurons in tissue culture are analyzed. Existing data about amytotic a way of formation two-nuclear neurons are critically considered. The conclusion becomes, that the mechanism of formation two-nuclear neurons is cellular fusion. Simultaneously the review confirms our representations about existence in nervous system sincitial interneural communications.

Aging changes in the nervous system

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... ency/article/004023.htm Aging changes in the nervous system To use the sharing features on this page, please enable JavaScript. The brain and nervous system are your body's central control center. They control ...

Central nervous system tumors

International Nuclear Information System (INIS)

Curran, W.J. Jr.

1991-01-01

Intrinsic tumors of the central nervous system (CNS) pose a particularly challenging problem to practicing oncologists. These tumors rarely metastasize outside the CNS, yet even histologically benign tumors can be life-threatening due to their local invasiveness and strategic location. The surrounding normal tissues of the nervous system is often incapable of full functional regeneration, therefore prohibiting aggressive attempts to use either complete surgical resection or high doses of irradiation. Despite these limitations, notable achievements have recently been recorded in the management of these tumors

Radiation injury to the nervous system

International Nuclear Information System (INIS)

Gutin, P.H.; Leibel, S.A.; Sneline, G.E.

1991-01-01

This book is designed to describe to the radiation biologist, radiation oncologist, neurologist, neurosurgeon, medical oncologist, and neuro-oncologist, the current state of knowledge about the tolerance of the nervous system to various kinds of radiation, the mechanisms of radiation injury, and how nervous system tolerance and injury are related to the more general problem of radiation damage to normal tissue of all types. The information collected here should stimulate interest in and facilitate the growing research effort into radiation injury to the nervous system

Your Brain and Nervous System

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... Safe Videos for Educators Search English Español Your Brain & Nervous System KidsHealth / For Kids / Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

Primary angiitis of the central nervous system: an ante-mortem diagnosis.

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Singh S

2000-10-01

Full Text Available A rare case of primary angiitis of the central nervous system (PACNS is reported with its clinical and magnetic resonance imaging (MRI features. A 20-year-old girl presented with headache, projectile vomiting, unsteadiness of gait and urgency of micturition. She had left seventh nerve upper motor neuron type paresis, increased tone in all four limbs, exaggerated deep tendon reflexes, cerebellar signs, and papilloedema. Cerebrospinal fluid showed lymphocytosis with elevated protein and normal glucose level. Cerebral computerised tomographic scan and MRI showed bilateral diffuse asymmetric supra- and infra-tentorial lesions (predominantly in the supratentorial and left cerebrum. On MRI, the lesions were hyperintense on T2, and proton density-weighted images and hypointense on T1-weighted images. Based on the clinical findings of raised intracranial tension and MRI features, initial diagnoses of gliomatosis cerebrii, tuberculous meningitis, primary central nervous system lymphoma and chronic viral encephalitis were considered. PACNS was not included in the initial differentials and, an open brain biopsy was advised which established the definitive diagnosis.

Peripheral nervous system insulin resistance in ob/ob mice

Science.gov (United States)

2013-01-01

Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

Serotonin neuron development: shaping molecular and structural identities.

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Deneris, Evan; Gaspar, Patricia

2018-01-01

The continuing fascination with serotonin (5-hydroxytryptamine, 5-HT) as a nervous system chemical messenger began with its discovery in the brains of mammals in 1953. Among the many reasons for this decades-long interest is that the small numbers of neurons that make 5-HT influence the excitability of neural circuits in nearly every region of the brain and spinal cord. A further reason is that 5-HT dysfunction has been linked to a range of psychiatric and neurological disorders many of which have a neurodevelopmental component. This has led to intense interest in understanding 5-HT neuron development with the aim of determining whether early alterations in their generation lead to brain disease susceptibility. Here, we present an overview of the neuroanatomical organization of vertebrate 5-HT neurons, their neurogenesis, and prodigious axonal architectures, which enables the expansive reach of 5-HT neuromodulation in the central nervous system. We review recent findings that have revealed the molecular basis for the tremendous diversity of 5-HT neuron subtypes, the impact of environmental factors on 5-HT neuron development, and how 5-HT axons are topographically organized through disparate signaling pathways. We summarize studies of the gene regulatory networks that control the differentiation, maturation, and maintenance of 5-HT neurons. These studies show that the regulatory factors controlling acquisition of 5-HT-type transmitter identity continue to play critical roles in the functional maturation and the maintenance of 5-HT neurons. New insights are presented into how continuously expressed 5-HT regulatory factors control 5-HT neurons at different stages of life and how the regulatory networks themselves are maintained. WIREs Dev Biol 2018, 7:e301. doi: 10.1002/wdev.301 This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and

Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway.

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Seii eOHKA

2012-04-01

Full Text Available In humans, paralytic poliomyelitis results from the invasion of the central nervous system by circulating poliovirus (PV via the blood-brain barrier (BBB. After the virus enters the central nervous system (CNS, it replicates in neurons, especially in motor neurons (MNs, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155-transgenic (Tg mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. Recently, we identified transferrin receptor 1 (TfR1 of mouse brain capillary endothelial cells as a binding protein to PV, implicating that TfR1 is a possible receptor for PV to permeate the BBB.

The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function.

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Annina Huser

Full Text Available The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naïve odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed.

Dietary Carotenoids and the Nervous System

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Billy R. Hammond

2015-12-01

Full Text Available This issue of Foods is focused on the general topic of carotenoids within the nervous system. The focus is on the effects of the xanthophylls on the central nervous system (CNS, reflecting the majority of work in this area. [...

Autoradiographic localization of thyrotropin releasing hormone (TRH) receptors in the central nervous system

International Nuclear Information System (INIS)

Manaker, S.

1985-01-01

Quantitative autoradiography was used to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat and human central nervous system (CNS). The binding of [ 3 H]-3-methyl-histidine 2 -TRH ([ 3 H]-MeTRH) to TRH receptors was saturable, of a high affinity (K/sub d/ = 5 nM), and specific for TRH analogs. Studies with neurotoxins ibotenic acid and 6-hydroxydopamine (6-OHDA) suggest that TRH receptors within the amygdala are predominantly located on cell bodies, and not nerve terminals. Finally, an examination was made of the concentrations of TRH receptors in spinal cords of patients with amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons located in Lamina IX. Large decreases in TRH receptors were noted in ALS spinal cords, when compared to non-neurological controls, probably reflecting the loss of motor neurons. In addition, decreases in the TRH receptor concentration of Lamina II were observed. This finding may reflect the sensitivity of neurons throughout the CNS to the pathophysiologic mechanisms of neuronal degeneration which cause ALS

Area 51: How do Acanthamoeba invade the central nervous system?

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Siddiqui, Ruqaiyyah; Emes, Richard; Elsheikha, Hany; Khan, Naveed Ahmed

2011-05-01

Acanthamoeba granulomatous encephalitis generally develops as a result of haematogenous spread, but it is unclear how circulating amoebae enter the central nervous system (CNS) and cause inflammation. At present, the mechanisms which Acanthamoeba use to invade this incredibly well-protected area of the CNS and produce infection are not well understood. In this paper, we propose two key virulence factors: mannose-binding protein and extracellular serine proteases as key players in Acanthamoeba traversal of the blood-brain barrier leading to neuronal injury. Both molecules should provide excellent opportunities as potential targets in the rational development of therapeutic interventions against Acanthamoeba encephalitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

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Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

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Eun-Mi Hur

2014-12-01

Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

The principal neuronal gD-type 3-O-sulfotransferases and their products in central and peripheral nervous system tissues

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Lawrence, Roger; Yabe, Tomio; HajMohammadi, Sassan; Rhodes, John; McNeely, Melissa; Liu, Jian; Lamperti, Edward D.; Toselli, Paul A.; Lech, Miroslaw; Spear, Patricia G.; Rosenberg, Robert D.; Shworak, Nicholas W.

2007-01-01

Within the nervous system, heparan sulfate (HS) of the cell surface and extracellular matrix influences developmental, physiologic and pathologic processes. HS is a functionally diverse polysaccharide that employs motifs of sulfate groups to selectively bind and modulate various effector proteins. Specific HS activities are modulated by 3-O-sulfated glucosamine residues, which are generated by a family of seven 3-O-sulfotransferases (3-OSTs). Most isoforms we herein designate as gD-type 3-OSTs because they generate HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of herpes simplex virus 1 (HSV-1) and thereby mediate viral cellular entry. Certain gD-type isoforms are anticipated to modulate neurobiologic events, because a Drosophila gD-type 3-OST is essential for a conserved neurogenic signaling pathway regulated by Notch. Information about 3-OST isoforms expressed in the nervous system of mammals is incomplete. Here, we identify the 3-OST isoforms having properties compatible with their participation in neurobiologic events. We show that 3-OST-2 and 3-OST-4 are principal isoforms of brain. We find these are gD-type enzymes, as they produce products similar to a prototypical gD-type isoform, and they can modify HS to generate receptors for HSV-1 entry into cells. Therefore, 3-OST-2 and 3-OST-4 catalyze modifications similar or identical to those made by the Drosophila gD-type 3-OST that has a role in regulating Notch signaling. We also find that 3-OST-2 and 3-OST-4 are the predominant isoforms expressed in neurons of the trigeminal ganglion, and 3-OST-2/4-type 3-O-sulfated residues occur in this ganglion and in select brain regions. Thus, 3-OST-2 and 3-OST-4 are the major neural gD-type 3-OSTs, and so are prime candidates for participating in HS-dependent neurobiologic events. PMID:17482450

Expression of RYamide in the nervous and endocrine system of Bombyx mori.

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Roller, Ladislav; Čižmár, Daniel; Bednár, Branislav; Žitňan, Dušan

2016-06-01

RYamides are neuropeptides encoded by a gene whose precise expression and function have not yet been determined. We identified the RYamide gene transcript (fmgV1g15f, SilkBase database) and predicted two candidates for G-protein coupled RYamide receptors (A19-BAG68418 and A22-BAG68421) in the silkworm Bombyx mori. We cloned the RYamide transcript and described its spatial expression using in situ hybridisation. In the larval central nervous system (CNS) expression of RYamide was restricted to 12-14 small neurons in the brain and two posterior neurons in the terminal abdominal ganglion. During metamorphosis their number decreased to eight protocerebral neurons in the adults. Multiple staining, using various insect neuropeptide antibodies, revealed that neurons expressing RYamide are different from other peptidergic cells in the CNS. We also found RYamide expression in the enteroendocrine cells (EC) of the anterior midgut of larvae, pupae and adults. Two minor subpopulations of these EC were also immunoreactive to antibodies against tachykinin and myosupressin. This expression pattern suggests RYamides may play a role in the regulation of feeding and digestion. Copyright © 2016 Elsevier Inc. All rights reserved.

The Central Nervous System of Box Jellyfish

DEFF Research Database (Denmark)

Garm, Anders Lydik; Ekström, Peter

2008-01-01

of behaviors in the box jellyfish such as obstacle avoidance and navigation. The need to process the visual information and turn it into the appropriate behavior puts strong demands on the nervous system of box jellyfish, which appears more elaborate than in other cnidarians. Here, the central part...... of this nervous system is described. Each rhopalium holds a separate part of the CNS with 1,000 nerve cells and a large amount of neuropil. The rhopalial nervous system has several subsystems defined by the anatomy, location, and immunocytochemistry of the cells. Most of the subsystems connect to one or more...... of the eye types, and it is likely that the rhopalial nervous system accounts for most of the visual processing. The major part of the CNS is made up of a ring nerve encircling the bell shaped body. The ring nerve holds around 10,000 cells and is directly connected to all four rhopalial nervous systems...

Genetic pathways for differentiation of the peripheral nervous system in ascidians

Science.gov (United States)

Waki, Kana; Imai, Kaoru S.; Satou, Yutaka

2015-01-01

Ascidians belong to tunicates, the sister group of vertebrates. Peripheral nervous systems (PNSs) including epidermal sensory neurons (ESNs) in the trunk and dorsal tail regions of ascidian larvae are derived from cells adjacent to the neural plate, as in vertebrates. On the other hand, peripheral ESNs in the ventral tail region are derived from the ventral ectoderm under the control of BMP signalling, reminiscent of sensory neurons of amphioxus and protostomes. In this study, we show that two distinct mechanisms activate a common gene circuit consisting of Msx, Ascl.b, Tox, Delta.b and Pou4 in the dorsal and ventral regions to differentiate ESNs. Our results suggest that ventral ESNs of the ascidian larva are not directly homologous to vertebrate PNSs. The dorsal ESNs might have arisen via co-option of the original PNS gene circuit to the neural plate border in an ancestral chordate. PMID:26515371

Diverse roles of extracellular calcium-sensing receptor in the central nervous system

DEFF Research Database (Denmark)

Bandyopadhyay, Sanghamitra; Tfelt-Hansen, Jacob; Chattopadhyay, Naibedya

2010-01-01

The G-protein-coupled calcium-sensing receptor (CaSR), upon activation by Ca(2+) or other physiologically relevant polycationic molecules, performs diverse functions in the brain. The CaSR is widely expressed in the central nervous system (CNS) and is characterized by a robust increase in its...... to astrocytic or neuronal lineages. In adult CNS, CaSR has broad relevance in maintaining local ionic homeostasis. CaSR shares an evolutionary relationship with the metabotropic glutamate receptor and forms heteromeric complexes with the type B-aminobutyric acid receptor subunits that affects its cell surface...

Immune and Inflammatory Responses in the Central Nervous System: Modulation by Astrocytes

DEFF Research Database (Denmark)

Penkowa, Milena; hidalgo, juan; aschner, michael

2008-01-01

Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

[Parasitic diseases of the central nervous system].

Science.gov (United States)

Schmutzhard, E

2010-02-01

Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.).

Rapid method for culturing embryonic neuron-glial cell cocultures

DEFF Research Database (Denmark)

Svenningsen, Åsa Fex; Shan, Wei-Song; Colman, David R

2003-01-01

neurons is seen after 3 weeks (2 weeks in ascorbic acid), suggesting that basal lamina production is important even for glial ensheathment in the enteric nervous system. No overgrowth of fibroblasts or other nonneuronal cells was noted in any cultures, and myelination of the peripheral nervous system...

Bidirectional communication between sensory neurons and osteoblasts in an in vitro coculture system.

Science.gov (United States)

Kodama, Daisuke; Hirai, Takao; Kondo, Hisataka; Hamamura, Kazunori; Togari, Akifumi

2017-02-01

Recent studies have revealed that the sensory nervous system is involved in bone metabolism. However, the mechanism of communication between neurons and osteoblasts is yet to be elucidated. In this study, we investigated the signaling pathways between sensory neurons of the dorsal root ganglion (DRG) and the osteoblast-like MC3T3-E1 cells using an in vitro coculture system. Our findings indicate that signal transduction from DRG-derived neurons to MC3T3-E1 cells is suppressed by antagonists of the AMPA receptor and the NK 1 receptor. Conversely, signal transduction from MC3T3-E1 cells to DRG-derived neurons is suppressed by a P2X 7 receptor antagonist. Our results suggest that these cells communicate with each other by exocytosis of glutamate, substance P in the efferent signal, and ATP in the afferent signal. © 2017 Federation of European Biochemical Societies.

New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in Alzheimer's Disease.

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Fuchsberger, Tanja; Lloret, Ana; Viña, Jose

2017-05-14

The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimer's disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder. Moreover, recently evidence has been provided for an inactivation of APC/C in AD. It has been shown that oligomers of the AD-related peptide, Aβ, induce degradation of the APC/C activator subunit cdh1, in vitro in neurons in culture and in vivo in the mouse hippocampus. Furthermore, in the AD mouse model APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when compared to age-matched wildtype mice. In this review, we provide a complete list of APC/C substrates that are involved in the nervous system and we discuss their functions. We also summarize recent studies that show neurobiological effects in cdh1 knockout mouse models. Finally, we discuss the role of APC/C in the pathophysiology of AD.

The receptor for Granulocyte-colony stimulating factor (G-CSF is expressed in radial glia during development of the nervous system

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Krüger Carola

2008-03-01

Full Text Available Abstract Background Granulocyte colony-stimulating (G-CSF factor is a well-known hematopoietic growth factor stimulating the proliferation and differentiation of myeloid progenitors. Recently, we uncovered that G-CSF acts also as a neuronal growth factor in the brain, which promotes adult neural precursor differentiation and enhances regeneration of the brain after insults. In adults, the receptor for G-CSF is predominantly expressed in neurons in many brain areas. We also described expression in neurogenic regions of the adult brain, such as the subventricular zone and the subgranular layer of the dentate gyrus. In addition, we found close co-localization of the G-CSF receptor and its ligand G-CSF. Here we have conducted a systematic expression analysis of G-CSF receptor and its ligand in the developing embryo. Results Outside the central nervous system (CNS we found G-CSF receptor expression in blood vessels, muscles and their respective precursors and neurons. The expression of the G-CSF receptor in the developing CNS was most prominent in radial glia cells. Conclusion Our data imply that in addition to the function of G-CSF and its receptor in adult neurogenesis, this system also has a role in embryonic neurogenesis and nervous system development.

Inwardly Rectifying Potassium (Kir) Channels Represent a Critical Ion Conductance Pathway in the Nervous Systems of Insects.

Science.gov (United States)

Chen, Rui; Swale, Daniel R

2018-01-25

A complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. The recent development of potent and selective small-molecule modulators of insect inward rectifier potassium (Kir) channels has enabled the interrogation of the physiological role and toxicological potential of Kir channels within various insect tissue systems. Therefore, we aimed to highlight the physiological and functional role of neural Kir channels the central nervous system, muscular system, and neuromuscular system through pharmacological and genetic manipulations. Our data provide significant evidence that Drosophila neural systems rely on the inward conductance of K + ions for proper function since pharmacological inhibition and genetic ablation of neural Kir channels yielded dramatic alterations of the CNS spike discharge frequency and broadening and reduced amplitude of the evoked EPSP at the neuromuscular junction. Based on these data, we conclude that neural Kir channels in insects (1) are critical for proper function of the insect nervous system, (2) represents an unexplored physiological pathway that is likely to shape the understanding of neuronal signaling, maintenance of membrane potentials, and maintenance of the ionic balance of insects, and (3) are capable of inducing acute toxicity to insects through neurological poisoning.

Nervous system examination on YouTube

Directory of Open Access Journals (Sweden)

Azer Samy A

2012-12-01

Full Text Available Abstract Background Web 2.0 sites such as YouTube have become a useful resource for knowledge and are used by medical students as a learning resource. This study aimed at assessing videos covering the nervous system examination on YouTube. Methods A research of YouTube was conducted from 2 November to 2 December 2011 using the following key words “nervous system examination”, “nervous system clinical examination”, “cranial nerves examination”, “CNS examination”, “examination of cerebellum”, “balance and coordination examination”. Only relevant videos in the English language were identified and related URL recorded. For each video, the following information was collected: title, author/s, duration, number of viewers, number of posted comments, and total number of days on YouTube. Using criteria comprising content, technical authority and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-educationally useful. Results A total of 2240 videos were screened; 129 were found to have relevant information to nervous system examination. Analysis revealed that 61 (47% of the videos provided useful information on the nervous system examination. These videos scored (mean ± SD, 14.9 ± 0.2 and mainly covered examination of the whole nervous system (8 videos, 13%, cranial nerves (42 videos, 69%, upper limbs (6 videos, 10%, lower limbs (3 videos, 5%, balance and co-ordination (2 videos, 3%. The other 68 (53% videos were not useful educationally; scoring (mean ± SD, 11.1 ± 3.0. The total viewers of all videos was 2,189,434. Useful videos were viewed by 1,050,445 viewers (48% of total viewers. The total viewership per day for useful videos was 1,794.5 and for non-useful videos 1,132.0. The differences between the three assessors were insignificant (less than 0.5 for the mean and 0.3 for the SD. Conclusions Currently, YouTube provides an adequate resource

Nervous system examination on YouTube

Science.gov (United States)

2012-01-01

Background Web 2.0 sites such as YouTube have become a useful resource for knowledge and are used by medical students as a learning resource. This study aimed at assessing videos covering the nervous system examination on YouTube. Methods A research of YouTube was conducted from 2 November to 2 December 2011 using the following key words “nervous system examination”, “nervous system clinical examination”, “cranial nerves examination”, “CNS examination”, “examination of cerebellum”, “balance and coordination examination”. Only relevant videos in the English language were identified and related URL recorded. For each video, the following information was collected: title, author/s, duration, number of viewers, number of posted comments, and total number of days on YouTube. Using criteria comprising content, technical authority and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-educationally useful. Results A total of 2240 videos were screened; 129 were found to have relevant information to nervous system examination. Analysis revealed that 61 (47%) of the videos provided useful information on the nervous system examination. These videos scored (mean ± SD, 14.9 ± 0.2) and mainly covered examination of the whole nervous system (8 videos, 13%), cranial nerves (42 videos, 69%), upper limbs (6 videos, 10%), lower limbs (3 videos, 5%), balance and co-ordination (2 videos, 3%). The other 68 (53%) videos were not useful educationally; scoring (mean ± SD, 11.1 ± 3.0). The total viewers of all videos was 2,189,434. Useful videos were viewed by 1,050,445 viewers (48% of total viewers). The total viewership per day for useful videos was 1,794.5 and for non-useful videos 1,132.0. The differences between the three assessors were insignificant (less than 0.5 for the mean and 0.3 for the SD). Conclusions Currently, YouTube provides an adequate resource for learning

Nervous system examination on YouTube.

Science.gov (United States)

Azer, Samy A; Aleshaiwi, Sarah M; Algrain, Hala A; Alkhelaif, Rana A

2012-12-22

Web 2.0 sites such as YouTube have become a useful resource for knowledge and are used by medical students as a learning resource. This study aimed at assessing videos covering the nervous system examination on YouTube. A research of YouTube was conducted from 2 November to 2 December 2011 using the following key words "nervous system examination", "nervous system clinical examination", "cranial nerves examination", "CNS examination", "examination of cerebellum", "balance and coordination examination". Only relevant videos in the English language were identified and related URL recorded. For each video, the following information was collected: title, author/s, duration, number of viewers, number of posted comments, and total number of days on YouTube. Using criteria comprising content, technical authority and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-educationally useful. A total of 2240 videos were screened; 129 were found to have relevant information to nervous system examination. Analysis revealed that 61 (47%) of the videos provided useful information on the nervous system examination. These videos scored (mean ± SD, 14.9 ± 0.2) and mainly covered examination of the whole nervous system (8 videos, 13%), cranial nerves (42 videos, 69%), upper limbs (6 videos, 10%), lower limbs (3 videos, 5%), balance and co-ordination (2 videos, 3%). The other 68 (53%) videos were not useful educationally; scoring (mean ± SD, 11.1 ± 3.0). The total viewers of all videos was 2,189,434. Useful videos were viewed by 1,050,445 viewers (48% of total viewers). The total viewership per day for useful videos was 1,794.5 and for non-useful videos 1,132.0. The differences between the three assessors were insignificant (less than 0.5 for the mean and 0.3 for the SD). Currently, YouTube provides an adequate resource for learning nervous system examination, which can be used by medical students

Immunosenescence of microglia and macrophages: impact on the ageing central nervous system.

Science.gov (United States)

Rawji, Khalil S; Mishra, Manoj K; Michaels, Nathan J; Rivest, Serge; Stys, Peter K; Yong, V Wee

2016-03-01

Ageing of the central nervous system results in a loss of both grey and white matter, leading to cognitive decline. Additional injury to both the grey and white matter is documented in many neurological disorders with ageing, including Alzheimer's disease, traumatic brain and spinal cord injury, stroke, and multiple sclerosis. Accompanying neuronal and glial damage is an inflammatory response consisting of activated macrophages and microglia, innate immune cells demonstrated to be both beneficial and detrimental in neurological repair. This article will propose the following: (i) infiltrating macrophages age differently from central nervous system-intrinsic microglia; (ii) several mechanisms underlie the differential ageing process of these two distinct cell types; and (iii) therapeutic strategies that selectively target these diverse mechanisms may rejuvenate macrophages and microglia for repair in the ageing central nervous system. Most responses of macrophages are diminished with senescence, but activated microglia increase their expression of pro-inflammatory cytokines while diminishing chemotactic and phagocytic activities. The senescence of macrophages and microglia has a negative impact on several neurological diseases, and the mechanisms underlying their age-dependent phenotypic changes vary from extrinsic microenvironmental changes to intrinsic changes in genomic integrity. We discuss the negative effects of age on neurological diseases, examine the response of senescent macrophages and microglia in these conditions, and propose a theoretical framework of therapeutic strategies that target the different mechanisms contributing to the ageing phenotype in these two distinct cell types. Rejuvenation of ageing macrophage/microglia may preserve neurological integrity and promote regeneration in the ageing central nervous system. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions

PERSPECTIVE: Electrical activity enhances neuronal survival and regeneration

Science.gov (United States)

Corredor, Raul G.; Goldberg, Jeffrey L.

2009-10-01

The failure of regeneration in the central nervous system (CNS) remains an enormous scientific and clinical challenge. After injury or in degenerative diseases, neurons in the adult mammalian CNS fail to regrow their axons and reconnect with their normal targets, and furthermore the neurons frequently die and are not normally replaced. While significant progress has been made in understanding the molecular basis for this lack of regenerative ability, a second approach has gained momentum: replacing lost neurons or lost connections with artificial electrical circuits that interface with the nervous system. In the visual system, gene therapy-based 'optogenetics' prostheses represent a competing technology. Now, the two approaches are converging, as recent data suggest that electrical activity itself, via the molecular signaling pathways such activity stimulates, is sufficient to induce neuronal survival and regeneration, particularly in retinal ganglion cells. Here, we review these data, discuss the effects of electrical activity on neurons' molecular signaling pathways and propose specific mechanisms by which exogenous electrical activity may be acting to enhance survival and regeneration.

Electrophysiological properties of neurons derived from human stem cells and iNeurons in vitro.

Science.gov (United States)

Halliwell, Robert F

2017-06-01

Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine. This review addresses the current state of our knowledge of functional receptors and ion channels expressed in neurons derived from human stem cells and iNeurons and identifies gaps and questions that might be investigated in future studies; it focusses almost exclusively on what is known about the electrophysiological properties of neurons derived from human stem cells and iN cells in vitro with an emphasis on voltage and ligand gated ion channels, since these mediate synaptic signalling in the nervous system and they are at the heart of neuropharmacology. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Central nervous system involvement in systemic lupus erythematosus - diagnosis and therapy].

Science.gov (United States)

Szmyrka, Magdalena

Nervous system involvement in lupus belongs to its severe complications and significantly impacts its prognosis. Neuropsychiatric lupus includes 19 disease manifestations concerning both central and peripheral nervous system. This paper presents clinical aspects of central nervous system involvement in lupus. It reviews its epidemiology, risk factors and principles of diagnosis and therapy.

Effect of exposure to anesthesia on the functions of nervous system of children in the growth period

Directory of Open Access Journals (Sweden)

Fei DENG

2015-04-01

Full Text Available With the update of concept of anesthesia and the improvement in anesthesia technology, an increasing number of children received surgical treatment under general anesthesia. Subsequently, the influence of anesthetic agents on the development of nervous system becomes a focused issue. Basic research found that anesthetic agents can lower the synaptic plasticity of nervous system, produce neuronal apoptosis and other neurodegenerative diseases during the vulnerable window period for brain development, thus affect learning and memory function when the children reach adulthood. Since 2007, a number of research centers around the world conducted a large-scale clinical study on this issue, but there are relevant studies showing that there is no direct correlation between the two. DOI: 10.11855/j.issn.0577-7402.2015.03.16

Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration.

Science.gov (United States)

Andersen, Hjalte Holm; Johnsen, Kasper Bendix; Moos, Torben

2014-05-01

Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS.

Zebrafish: an exciting model for investigating the spatio-temporal pattern of enteric nervous system development.

LENUS (Irish Health Repository)

Doodnath, Reshma

2012-02-01

AIM: Recently, the zebrafish (Danio rerio) has been shown to be an excellent model for human paediatric research. Advantages over other models include its small size, externally visually accessible development and ease of experimental manipulation. The enteric nervous system (ENS) consists of neurons and enteric glia. Glial cells permit cell bodies and processes of neurons to be arranged and maintained in a proper spatial arrangement, and are essential in the maintenance of basic physiological functions of neurons. Glial fibrillary acidic protein (GFAP) is expressed in astrocytes, but also expressed outside of the central nervous system. The aim of this study was to investigate the spatio-temporal pattern of GFAP expression in developing zebrafish ENS from 24 h post-fertilization (hpf), using transgenic fish that express green fluorescent protein (GFP). METHODS: Zebrafish embryos were collected from transgenic GFP Tg(GFAP:GFP)(mi2001) adult zebrafish from 24 to 120 hpf, fixed and processed for whole mount immunohistochemistry. Antibodies to Phox2b were used to identify enteric neurons. Specimens were mounted on slides and imaging was performed using a fluorescent laser confocal microscope. RESULTS: GFAP:GFP labelling outside the spinal cord was identified in embryos from 48 hpf. The patterning was intracellular and consisted of elongated profiles that appeared to migrate away from the spinal cord into the periphery. At 72 and 96 hpf, GFAP:GFP was expressed dorsally and ventrally to the intestinal tract. At 120 hpf, GFAP:GFP was expressed throughout the intestinal wall, and clusters of enteric neurons were identified using Phox2b immunofluorescence along the pathway of GFAP:GFP positive processes, indicative of a migratory pathway of ENS precursors from the spinal cord into the intestine. CONCLUSION: The pattern of migration of GFAP:GFP expressing cells outside the spinal cord suggests an organized, early developing migratory pathway to the ENS. This shows for the

Neurons other than motor neurons in motor neuron disease.

Science.gov (United States)

Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

2017-11-01

Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

Central nervous system mesenchymal chondrosarcoma

Energy Technology Data Exchange (ETDEWEB)

Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Caroli, E. [Policlinico S. Andrea, Rome (Italy). Dept. of Neurological Sciences, Neurosurgery

2005-06-15

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Central nervous system mesenchymal chondrosarcoma

International Nuclear Information System (INIS)

Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F.; Caroli, E.

2005-01-01

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival

Diffusion tensor analysis with nuclear magnetic resonance in human central nervous system

International Nuclear Information System (INIS)

Nakayama, Naoki

1998-01-01

Nuclear magnetic resonance has been used to measure the diffusivity of water molecules. In central nervous system, anisotropic diffusion, which is characterized by apparent diffusion tensor D app ξ , is thought to be related to neuronal fiber tract orientation. For precise observation of anisotropic diffusion, it is needed to determine the diagonal and off-diagonal elements of D app ξ . Once D app ξ is estimated from a series of diffusion weighted images, a tissue's orthotropic principal axes and diffusivity of each direction are determined from eigenvalues and eigenvectors of D app ξ . There are several methods to represent anisotropic diffusion with D app ξ . Examples are diffusion ellipsoids constructed in each voxel depicting both these principal axes and the mean diffusion length in these directions, trace invariant values and its mapping image, largest eigenvalue, and ratio of largest eigenvalue to the other eigenvalue. In this study, the author investigated practical procedure to analyze diffusion tensor D app ξ using both of spin-echo end echo-planer diffusion weighted imagings with 3-tesla magnetic resonance machine in human brain. The ellipsoid representation provided particularly useful information about microanatomy including neuronal fiber tract orientation and molecular mobility reflective of microstructure. Furthermore, in the lesion of Wallerian degeneration, the loss of anisotropy of local apparent diffusion was observed. It is suggested that the function of axons can be observed via degree of anisotropy of apparent diffusion. Consequently, diffusion tensor analysis is expected to be a powerful, noninvasive method capable of quantitative and functional evaluation of the central nervous system. (author)

Do enteric neurons make hypocretin? ☆

OpenAIRE

Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

2007-01-01

Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, s...

C. elegans model of neuronal aging

OpenAIRE

Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min; Pan, Chun-Liang

2011-01-01

Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and...

The effect of space radiation of the nervous system

Science.gov (United States)

Gauger, Grant E.; Tobias, Cornelius A.; Yang, Tracy; Whitney, Monroe

The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.

Out of time: a possible link between mirror neurons, autism and electromagnetic radiation.

Science.gov (United States)

Thornton, Ian M

2006-01-01

Recent evidence suggests a link between autism and the human mirror neuron system. In this paper, I argue that temporal disruption from the environment may play an important role in the observed mirror neuron dysfunction, leading in turn to the pattern of deficits associated with autism. I suggest that the developing nervous system of an infant may be particularly prone to temporal noise that can interfere with the initial calibration of brain networks such as the mirror neuron system. The most likely source of temporal noise in the environment is artificially generated electromagnetic radiation. To date, there has been little evidence that electromagnetic radiation poses a direct biological hazard. It is clear, however, that time-varying electromagnetic waves have the potential to temporally modulate the nervous system, particularly when populations of neurons are required to act together. This modulation may be completely harmless for the fully developed nervous system of an adult. For an infant, this same temporal disruption might act to severely delay or disrupt vital calibration processes.

Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of Lamp-2-deficient mice.

Science.gov (United States)

Furuta, Akiko; Kikuchi, Hisae; Fujita, Hiromi; Yamada, Daisuke; Fujiwara, Yuuki; Kabuta, Tomohiro; Nishino, Ichizo; Wada, Keiji; Uchiyama, Yasuo

2015-06-01

Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ultrastructural studies, we found various-shaped accumulations, including lipofuscin, glycolipid-like materials, and membranous structures, in the neurons and glial cells of Lamp-2-deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte lysosomes but were not observed in neurons. These pathological features indicate lysosomal storage disease; however, the findings are unlikely a consequence of deficiency of a single lysosomal enzyme. Although previous study results have shown a large amount of autophagic vacuoles in parenchymal cells of the visceral organs, these findings were rarely detected in the brain tissue except for some axons in the substantia nigra, in which abundant activated microglial cells with increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous system has a possible role in the degradation of the various macromolecules in lysosomes and an additional function concerning protection from oxidative stress, especially in the substantia nigra. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Developmental wiring of specific neurons is regulated by RET-1/Nogo-A in Caenorhabditis elegans

DEFF Research Database (Denmark)

Torpe, Nanna; Nørgaard, Steffen; Høye, Anette M.

2017-01-01

Nogo-A is a membrane-bound protein that functions to inhibit neuronal migration, adhesion, and neurite outgrowth during development. In the mature nervous system, Nogo-A stabilizes neuronal wiring to inhibit neuronal plasticity and regeneration after injury. Here, we show that RET-1, the sole Nog...... present a previously unidentified function for RET-1 in the nervous system of C. elegans.......-A homolog in Caenorhabditis elegans, is required to control developmental wiring of a specific subset of neurons. In ret-1 deletion mutant animals, specific ventral nerve cord axons are misguided where they fail to respect the ventral midline boundary. We found that ret-1 is expressed in multiple neurons...

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Nakadai, Taeko; Khono, Yukio

2006-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using human embryonal carcinoma (Ntera2=NT2) and Human neuroblastoma cell (NB1). They exposed to heavy ions and X ray 80% confluent cells in culture bottles. The cells were different type about growth and differentiation in the neuron. The apoptosis profile was measured by AnnexinV-EGFP, PI stained and fluorescence-activated cell sorter (FACS). Memory and learning function of adult mice were studied using water maze test after carbon- or iron-ion irradiation. Memory functions were rapidly decreased after irradiation both ions. Iron -ion group were recovered 20 weeks after irradiation C-ion group were recovered 25 weeks after irradiation. Tier memory were still keep at over 100 weeks after irradiation. (author)

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

Science.gov (United States)

Sakakibara, Yasufumi; Sekiya, Michiko; Fujisaki, Naoki; Quan, Xiuming; Iijima, Koichi M

2018-01-01

Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

Directory of Open Access Journals (Sweden)

Yasufumi Sakakibara

2018-01-01

Full Text Available Wolfram syndrome (WS, caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1, is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Understanding and controlling the enteric nervous system

NARCIS (Netherlands)

Boeckxstaens, G. E.

2002-01-01

The enteric nervous system or the `Little Brain' of the gut controls gastrointestinal motility and secretion, and is involved in visceral sensation. In this chapter, new developments in understanding the function of the enteric nervous system are described. In particular, the interaction of this

[Electromagnetic radiation of non-thermal intensity and short exposition as a sub-threshold irritant for the central nervous system].

Science.gov (United States)

Luk'ianova, S N

2013-01-01

This work represents generalization and the analysis of the long-term own materials characterizing reaction of the brain on electromagnetic radiation of low intensity (energy flow density in the continuous regime or in the impulse approximately 500 microW/sm2) and a short exposition (approximately 30 min). A set of the experimental results received on separate neurons, formations and brain as a whole give an idea about the reaction of the central nervous system to the studied influence. Comparison of these data with the corresponding responses to the known incentives (light, sound, electric current) testifies to the electromagnetic radiation of low energy flow density and a short exposition as a sub-threshold irritant for the central nervous system.

Secretin and autism: a basic morphological study about the distribution of secretin in the nervous system.

Science.gov (United States)

Köves, Katalin; Kausz, Mária; Reser, Diana; Illyés, György; Takács, József; Heinzlmann, Andrea; Gyenge, Eszter; Horváth, Károly

2004-12-15

For the first time, the relationship between secretin and autism has been demonstrated by one of us. Intravenous administration of secretin in autistic children caused a fivefold higher pancreaticobiliary fluid secretion than in healthy ones and, at least in some of the patients, better mental functions were reported after the secretin test. Because the precise localization of secretin in the brain is still not completely known, the abovementioned observation led us to map secretin immunoreactivity in the nervous system of several mammalian species. In the present work, the distribution of secretin immunoreactivity in cat and human nervous systems was compared with that of rats using an immunohistochemical approach. Secretin immunoreactivity was observed in the following brain structures of both humans and in colchicine-treated rats: (1) Purkinje cells in the cerebellar cortex; (2) central cerebellar nuclei; (3) pyramidal cells in the motor cortex; and (4) primary sensory neurons. Additionally, secretin immnoreactive cells were observed in the human hippocampus and amygdala and in third-order sensory neurons of the rat auditory system. In cats, secretin was only observed in the spinal ganglia. Our findings support the view that secretin is not only a gastrointestinal peptide but that it is also a neuropeptide. Its presence or the lack of its presence may have a role in the development of behavioral disorders.

Pericyte function in the physiological central nervous system.

Science.gov (United States)

Muramatsu, Rieko; Yamashita, Toshihide

2014-01-01

Damage to the central nervous system (CNS) leads to disruption of the vascular network, causing vascular dysfunction. Vascular dysfunction is the major event in the pathogenesis of CNS diseases and is closely associated with the severity of neuronal dysfunction. The suppression of vascular dysfunction has been considered a promising avenue to limit damage to the CNS, leading to efforts to clarify the cellular and molecular basis of vascular homeostasis maintenance. A reduction of trophic support and oxygen delivery due to circulatory insufficiency has long been regarded as a major cause of vascular damage. Moreover, recent studies provide a new perspective on the importance of the structural stability of blood vessels in CNS diseases. This updated article discusses emerging information on the key role of vascular integrity in CNS diseases, specially focusing on pericyte function. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Reelin signaling in the migration of ventral brain stem and spinal cord neurons

Directory of Open Access Journals (Sweden)

Sandra eBlaess

2016-03-01

Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

Hypoxia-inducible factor signalling mechanisms in the central nervous system.

Science.gov (United States)

Corcoran, A; O'Connor, J J

2013-08-01

In the CNS, neurones are highly sensitive to the availability of oxygen. In conditions where oxygen availability is decreased, neuronal function can be altered, leading to injury and cell death. Hypoxia has been implicated in a number of central nervous system pathologies including stroke, head trauma and neurodegenerative diseases. Cellular responses to oxygen deprivation are complex and result in activation of short- and long-term mechanisms to conserve energy and protect cells. Failure of synaptic transmission can be observed within minutes following this hypoxia. The acute effects of hypoxia on synaptic transmission are primarily mediated by altering ion fluxes across membranes, pre-synaptic effects of adenosine and other actions at glutamatergic receptors. A more long-term feature of the response of neurones to hypoxia is the activation of transcription factors such as hypoxia-inducible factor. The activation of hypoxia-inducible factor is governed by a family of dioxygenases called hypoxia-inducible factor prolyl 4 hydroxylases (PHDs). Under hypoxic conditions, PHD activity is inhibited, thereby allowing hypoxia-inducible factor to accumulate and translocate to the nucleus, where it binds to the hypoxia-responsive element sequences of target gene promoters. Inhibition of PHD activity stabilizes hypoxia-inducible factor and other proteins thus acting as a neuroprotective agent. This review will focus on the response of neuronal cells to hypoxia-inducible factor and its targets, including the prolyl hydroxylases. We also present evidence for acute effects of PHD inhibition on synaptic transmission and plasticity in the hippocampus. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Chapter 1. Central nervous system

International Nuclear Information System (INIS)

Planiol, T.; Veyre, A.; Plagne, R.

1975-01-01

The present situation with regard to explorations of the central nervous system by radioactive compounds is reviewed. For the sake of clarity the brain and cerebrospinal fluid examinations are described separately, with emphasis nevertheless on their complementarity. The tracers used in each of these examinations are listed, together with the criteria governing their choice. The different techniques employed are described. Scintigraphy is presented apart from gamma-angio-encephalography since it is not possible with rectilinear scintigraphs to observe the circulatory phase. The results are interpreted by an analysis of normal and pathological aspects of the different stages of the central nervous system [fr

Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis

Directory of Open Access Journals (Sweden)

Pengjiao Xi

2018-05-01

Full Text Available Background/Aims: Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. Methods: Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 108 or 2.0 × 1010 vector genomes or Control-AAV-EGFP (2.0 × 108 vector genomes was injected into the third ventricle. After administration, the rats were fed a high-fat diet (HFD for 9 weeks to induce obesity. Rats fed a chow fat diet were used as normal controls. Results: LKB1 delivery decreased body weight, energy intake, fat mass, and serum lipid levels. LKB1 also improved HFD-induced hepatic fatty degeneration. Interestingly, LKB1 over-expression in the hypothalamus activated the AMPK-POMC neurons-sympathetic nervous system (SNS axis, which can release epinephrine to promote white fat browning. Conversely, the elevated expression of MC3R/MC4R inhibited food intake. These two factors worked together to inhibit the development of obesity. Conclusions: LKB1 in the hypothalamus may have therapeutic potential for DIO through the activation of the AMPK-POMC neurons-SNS axis.

Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis.

Science.gov (United States)

Xi, Pengjiao; Du, Jianying; Liang, Huimin; Han, Jie; Wu, Zhaoxia; Wang, Haomin; He, Lu; Wang, Qiming; Ge, Haize; Li, Yongmei; Xue, Jie; Tian, Derun

2018-01-01

Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO) is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 108 or 2.0 × 1010 vector genomes) or Control-AAV-EGFP (2.0 × 108 vector genomes) was injected into the third ventricle. After administration, the rats were fed a high-fat diet (HFD) for 9 weeks to induce obesity. Rats fed a chow fat diet were used as normal controls. LKB1 delivery decreased body weight, energy intake, fat mass, and serum lipid levels. LKB1 also improved HFD-induced hepatic fatty degeneration. Interestingly, LKB1 over-expression in the hypothalamus activated the AMPK-POMC neurons-sympathetic nervous system (SNS) axis, which can release epinephrine to promote white fat browning. Conversely, the elevated expression of MC3R/MC4R inhibited food intake. These two factors worked together to inhibit the development of obesity. LKB1 in the hypothalamus may have therapeutic potential for DIO through the activation of the AMPK-POMC neurons-SNS axis. © 2018 The Author(s). Published by S. Karger AG, Basel.

PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

DEFF Research Database (Denmark)

Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L

2009-01-01

in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

3D printed nervous system on a chip.

Science.gov (United States)

Johnson, Blake N; Lancaster, Karen Z; Hogue, Ian B; Meng, Fanben; Kong, Yong Lin; Enquist, Lynn W; McAlpine, Michael C

2016-04-21

Bioinspired organ-level in vitro platforms are emerging as effective technologies for fundamental research, drug discovery, and personalized healthcare. In particular, models for nervous system research are especially important, due to the complexity of neurological phenomena and challenges associated with developing targeted treatment of neurological disorders. Here we introduce an additive manufacturing-based approach in the form of a bioinspired, customizable 3D printed nervous system on a chip (3DNSC) for the study of viral infection in the nervous system. Micro-extrusion 3D printing strategies enabled the assembly of biomimetic scaffold components (microchannels and compartmented chambers) for the alignment of axonal networks and spatial organization of cellular components. Physiologically relevant studies of nervous system infection using the multiscale biomimetic device demonstrated the functionality of the in vitro platform. We found that Schwann cells participate in axon-to-cell viral spread but appear refractory to infection, exhibiting a multiplicity of infection (MOI) of 1.4 genomes per cell. These results suggest that 3D printing is a valuable approach for the prototyping of a customized model nervous system on a chip technology.

Low-frequency electromagnetic radiation field interaction with cerebral nervous MT

International Nuclear Information System (INIS)

Gao Feng; Zhou Yi; Xiao Detao; Zhang Dengyu

2009-01-01

We investigate the interaction characteristics and mechanism of electromagnetic radiation field and cerebral nervous system. When the electromagnetic radiation is non-ionization low-frequency electromagnetic field, the two-state physical system in the cytoskeletal microtubule (MT) can be quantized. The state of information bits in cerebral neurons system is described by density matrix, and the system dynamics equation is established and solved. It indicates that when the brain is exposed to non-ionization low-frequency electromagnetic field, the density matrix non-opposite angle element of cerebral nervous qubit will never be zero, its quantum coherence characteristic can keep well, and the brain function will also be not damaged. (authors)

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

Science.gov (United States)

Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

2017-04-01

Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

A pupal transcriptomic screen identifies Ral as a target of store-operated calcium entry in Drosophila neurons.

Science.gov (United States)

Richhariya, Shlesha; Jayakumar, Siddharth; Abruzzi, Katharine; Rosbash, Michael; Hasan, Gaiti

2017-02-14

Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase. Disruption of Ral function in neurons impaired flight, whereas ectopic expression of Ral in SOCE-compromised neurons restored flight. Through live imaging of calcium transients from cultured pupal neurons, we confirmed that Ral does not participate in SOCE, but acts downstream of it. These results identify neuronal SOCE as a mechanism that regulates expression of specific genes during development of the pupal nervous system and emphasizes the relevance of SOCE-regulated gene expression to flight circuit maturation.

Thyroid Hormone in the CNS: Contribution of Neuron-Glia Interaction.

Science.gov (United States)

Noda, Mami

2018-01-01

The endocrine system and the central nervous system (CNS) are intimately linked. Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the regulation of development and differentiation of neurons and neuroglia and hence for development and function of the CNS. T3 (3,3',5-triiodothyronine), an active form of TH, is important not only for neuronal development but also for differentiation of astrocytes and oligodendrocytes, and for microglial development. In adult brain, T3 affects glial morphology with sex- and age-dependent manner and therefore may affect their function, leading to influence on neuron-glia interaction. T3 is an important signaling factor that affects microglial functions such as migration and phagocytosis via complex mechanisms. Therefore, dysfunction of THs may impair glial function as well as neuronal function and thus disturb the brain, which may cause mental disorders. Investigations on molecular and cellular basis of hyperthyroidism and hypothyroidism will help us to understand changes in neuron-glia interaction and therefore consequent psychiatric symptoms. © 2018 Elsevier Inc. All rights reserved.

Toxic effects of lead on neuronal development and function

International Nuclear Information System (INIS)

Freedman, R.; Olson, L.; Hoffer, B.J.

1990-01-01

The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. The goal of the authors research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. To study neuronal development in a system that minimizes such difficulties, the authors have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development in the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Using this system, they have discovered that lead induces a hypernoradrenergic innervation of central nervous system tissue. The increased innervation is observed not only structurally, but also functionally. Since norepinephrine is an inhibitory neurotransmitter, this ingrowth may explain the profound slowing of discharge of cerebellar neurons recorded in grafts of lead-treated animals. Studies in other tissues suggest that increased axonal ingrowth may be a general problem of lead intoxication that encompasses many brain areas, as well as peripheral sympathetic systems

Brain and Nervous System

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Brain and Nervous System KidsHealth / For Parents / Brain and ... healthy, and remove waste products. All About the Brain The brain is made up of three main ...

Stochastic models for spike trains of single neurons

CERN Document Server

Sampath, G

1977-01-01

1 Some basic neurophysiology 4 The neuron 1. 1 4 1. 1. 1 The axon 7 1. 1. 2 The synapse 9 12 1. 1. 3 The soma 1. 1. 4 The dendrites 13 13 1. 2 Types of neurons 2 Signals in the nervous system 14 2. 1 Action potentials as point events - point processes in the nervous system 15 18 2. 2 Spontaneous activi~ in neurons 3 Stochastic modelling of single neuron spike trains 19 3. 1 Characteristics of a neuron spike train 19 3. 2 The mathematical neuron 23 4 Superposition models 26 4. 1 superposition of renewal processes 26 4. 2 Superposition of stationary point processe- limiting behaviour 34 4. 2. 1 Palm functions 35 4. 2. 2 Asymptotic behaviour of n stationary point processes superposed 36 4. 3 Superposition models of neuron spike trains 37 4. 3. 1 Model 4. 1 39 4. 3. 2 Model 4. 2 - A superposition model with 40 two input channels 40 4. 3. 3 Model 4. 3 4. 4 Discussion 41 43 5 Deletion models 5. 1 Deletion models with 1nd~endent interaction of excitatory and inhibitory sequences 44 VI 5. 1. 1 Model 5. 1 The basic de...

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Liu Cuihua; Nagaoka, Shunji

2003-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using mouse neonatal brain cells in culture exposed to heavy ions and X ray at fifth days of the culture. The subsequent biological effects were evaluated by an induction of apoptosis and the survivability of neurons focusing on the dependencies of the animal strains with different genetic types, and linear energy transfer (LET) of the different nucleons. Of the three mouse strains tested, severe combined immunodeficiency (SCID), B6 and C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to both X-ray and carbon ion (290 MeV/n) when compared by 10% apoptotic induction. The LET dependency was compared with using SCID cells exposing to different ions, (X, C, Si, Ar, and Fe). Although no detectable LET dependency was observed at higher dose than 1 Gy, an enhancement was observed in the high LET region and at lower dose than 0.5 Gy. The survivability profiles of the neurons were different in the mouse strains and ions. Memory and learning function of adult mice were studied using water maze test after localized carbon- or iron-ion irradiation to hippocampus area. (author)

Glucose, epithelium, and enteric nervous system: dialogue in the dark.

Science.gov (United States)

Pfannkuche, H; Gäbel, G

2009-06-01

The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

Science.gov (United States)

Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

2016-02-01

In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice.

Science.gov (United States)

Liu, Jessica Ai-Jia; Lai, Frank Pui-Ling; Gui, Hong-Sheng; Sham, Mai-Har; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Hui, Chi-Chung; Ngan, Elly Sau-Wai

2015-12-01

Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). Aberrant hedgehog signaling disrupts NCC differentiation and might cause Hirschsprung disease. We performed genetic analyses to determine whether hedgehog signaling is involved in pathogenesis. We performed deep-target sequencing of DNA from 20 patients with Hirschsprung disease (16 men, 4 women), and 20 individuals without (controls), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10. Biological effects of GLI mutations were tested in luciferase reporter assays using HeLa or neuroblastoma cell lines. Development of the enteric nervous system was studied in Sufu(f/f), Gli3(Δ699), Wnt1-Cre, and Sox10(NGFP) mice using immunohistochemical and whole-mount staining procedures to quantify enteric neurons and glia and analyze axon fasciculation, respectively. NCC migration was studied using time-lapse imaging. We identified 3 mutations in GLI in 5 patients with Hirschsprung disease but no controls; all lead to increased transcription of SOX10 in cell lines. SUFU, GLI, and SOX10 form a regulatory loop that controls the neuronal vs glial lineages and migration of NCCs. Sufu mutants mice had high Gli activity, due to loss of Sufu, disrupting the regulatory loop and migration of enteric NCCs, leading to defective axonal fasciculation, delayed gut colonization, or intestinal hypoganglionosis. The ratio of enteric neurons to glia correlated inversely with Gli activity. We identified mutations that increase GLI activity in patients with Hirschsprung disease. Disruption of the SUFU-GLI-SOX10 regulatory loop disrupts migration of NCCs and development of the enteric nervous system in mice. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Acute irradiation injury and autonomic nervous system. 2

International Nuclear Information System (INIS)

Matsuu, Mutsumi; Sekine, Ichiro; Shichijo, Kazuko; Ito, Masahiro; Ikeda, Yuzi; Matsuzaki, Sumihiro; Zea-Iriate, W.-L.; Kondo, Takahito

1996-01-01

In order to elucidate the mechanism of occurrence of radiation sickness, whole body irradiation of various doses of X-ray was done on male spontaneously hypertensive rats (SHR) whose sympathetic nervous system is functionally activated and on their original male Wistar Kyoto rats (WKY) and the change of their body weights was examined. Further, changes of blood pressure in rats irradiated at 7.5 Gy, of norepinephrine contents in their gut as a parameter of sympathetic nervous function and of acetylcholine contents as that of parasympathetic nervous function were measured. Histopathological examinations were also performed. SHR died at smaller dose than WKY. The blood pressure as a parameter of systemic sympathetic nervous system varied greatly in SHR. Norepinephrine contents elevated rapidly and greatly in SHR after irradiation and acetylcholine contents rapidly elevated in WKY. Apoptosis was more frequently observed in the intestinal crypt of SHR. Participation of autonomic nervous system was thus shown in the appearance of acute radiation injury and sickness in SHR, which was thought to be a useful model for the investigation. (K.H.)

Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

Science.gov (United States)

Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

2016-01-12

The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

Gene Expression and the Diversity of Identified Neurons

OpenAIRE

Buck, L.; Stein, R.; Palazzolo, M.; Anderson, D. J.; Axel, R.

1983-01-01

Nervous systems consist of diverse populations of neurons that are anatomically and functionally distinct. The diversity of neurons and the precision with which they are interconnected suggest that specific genes or sets of genes are activated in some neurons but not expressed in others. Experimentally, this problem may be considered at two levels. First, what is the total number of genes expressed in the brain, and how are they distributed among the different populations of neurons? Second, ...

PIKfyve mediates the motility of late endosomes and lysosomes in neuronal dendrites.

Science.gov (United States)

Tsuruta, Fuminori; Dolmetsch, Ricardo E

2015-09-25

The endosome/lysosome system in the nervous system is critically important for a variety of neuronal functions such as neurite outgrowth, retrograde transport, and synaptic plasticity. In neurons, the endosome/lysosome system is crucial for the activity-dependent internalization of membrane proteins and contributes to the regulation of lipid level on the plasma membrane. Although homeostasis of membrane dynamics plays important roles in the properties of central nervous systems, it has not been elucidated how endosome/lysosome system is regulated. Here, we report that phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) mediates the motility of late endosomes and lysosomes in neuronal dendrites. Endosomes and lysosomes are highly motile in resting neurons, however knockdown of PIKfyve led to a significant reduction in late endosomes and lysosomes motility. We also found that vesicle acidification is crucial for their motility and PIKfyve is associated with this process indirectly. These data suggest that PIKfyve mediates vesicle motility through the regulation of vesicle integrity in neurons. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

What Health-Related Functions Are Regulated by the Nervous System?

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... What health-related functions are regulated by the nervous system? The nervous system plays a role in nearly every aspect of ... feeling emotions. Functions that are regulated by the nervous system include (but are not limited to): Brain growth ...

Central nervous system complications after liver transplantation.

Science.gov (United States)

Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

2015-08-01

We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

Directory of Open Access Journals (Sweden)

Anne Abot

2018-04-01

Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

Model of Artificial Intelligence Medium and its Use in Treating Disorders of the Nervous System

OpenAIRE

Shumilov Vladimir

2016-01-01

The work is devoted to modeling of the nervous system, the brain. The article considers the mechanism of formation of event traces fixed in the brain in the form of connections between neurons and the effect of these traces on the later passage of signals through the brain. That is, the influence of experience (traces) of previous events on the organism’s reaction by forecasting upcoming events. This «forecast» and anticipatory avoidance of dangers based on traces of previous events makes the...

Kalrn plays key roles within and outside of the nervous system

Directory of Open Access Journals (Sweden)

Mandela Prashant

2012-11-01

Full Text Available Abstract Background The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. Results We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO; transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Conclusions Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system.

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.

Science.gov (United States)

Annis, Ryan P; Swahari, Vijay; Nakamura, Ayumi; Xie, Alison X; Hammond, Scott M; Deshmukh, Mohanish

2016-12-01

Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of prodeath BH3-only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long-term survival. © 2016 Federation of European Biochemical Societies.

Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

Science.gov (United States)

Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

2018-05-05

Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

The biophysics of neuronal growth

International Nuclear Information System (INIS)

Franze, Kristian; Guck, Jochen

2010-01-01

For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

Myosin Va associates with mRNA in ribonucleoprotein particles present in myelinated peripheral axons and in the central nervous system.

Science.gov (United States)

Calliari, Aldo; Farías, Joaquina; Puppo, Agostina; Canclini, Lucía; Mercer, John A; Munroe, David; Sotelo, José R; Sotelo-Silveira, José R

2014-03-01

Sorting of specific mRNAs to particular cellular locations and regulation of their translation is an essential mechanism underlying cell polarization. The transport of RNAs by kinesins and dyneins has been clearly established in several cell models, including neurons in culture. A similar role appears to exist in higher eukaryotes for the myosins. Myosin Va (Myo5a) has been described as a component of ribonucleoprotein particles (RNPs) in the adult rat nervous system and associated to ZBP1 and ribosomes in ribosomal periaxoplasmic plaques (PARPs), making it a likely candidate for mediating some aspects of RNA transport in neurons. To test this hypothesis, we have characterized RNPs containing Myo5a in adult brains of rats and mice. Microarray analysis of RNAs co-immunoprecipitated with Myo5a indicates that this motor may associate with a specific subpopulation of neuronal mRNAs. We found mRNAs encoding α-synuclein and several proteins with functions in translation in these RNPs. Immunofluorescence analyses of RNPs showed apparent co-localization of Myo5a with ribosomes, mRNA and RNA-binding proteins in discrete structures present both in axons of neurons in culture and in myelinated fibers of medullary roots. Our data suggest that PARPs include RNPs bearing the mRNA coding for Myo5a and are equipped with kinesin and Myo5a molecular motors. In conclusion, we suggest that Myo5a is involved in mRNA trafficking both in the central and peripheral nervous systems. Copyright © 2013 Wiley Periodicals, Inc.

Comparative morphology of serotonergic-like immunoreactive elements in the central nervous system of kinorhynchs (Kinorhyncha, Cyclorhagida).

Science.gov (United States)

Herranz, María; Pardos, Fernando; Boyle, Michael J

2013-03-01

Cycloneuralian taxa exhibit similar organ system architectures, providing informative characters of metazoan evolution, yet very few modern comparative descriptions of cellular and molecular homologies within and among those taxa are available. We immunolabeled and characterized elements of the serotonergic nervous system in the kinorhynchs Echinoderes spinifurca, Antygomonas paulae, and Zelinkaderes brightae using confocal laser scanning microscopy. Fluorescent markers targeting DNA were combined with observations of auto-fluorescent structures to guide interpretations of the internal and external anatomy in each species. Results show a common pattern of the central nervous system with a circumenteric brain divided into ring-shaped anterior and posterior neuronal somata and a central neuropil connected to a multi-stringed, longitudinal ventral nerve cord. Structural similarities and differences in the nervous systems of these species were observed and described, stressing the incomplete ring nature of the anterior region of the kinorhynch brain, the functional relationship between the brain and the movable introvert, and the number and arrangement of nerve strings and somata of the ventral nerve cord. The ventral cord ends in two ventrolateral cell bodies in E. spinifurca, and forms a terminal loop associated with a midterminal spine in A. paulae and Z. brightae. The possible functional and phylogenetic significance of these features and arrangements are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Towards a general theory of neural computation based on prediction by single neurons.

Directory of Open Access Journals (Sweden)

Christopher D Fiorillo

Full Text Available Although there has been tremendous progress in understanding the mechanics of the nervous system, there has not been a general theory of its computational function. Here I present a theory that relates the established biophysical properties of single generic neurons to principles of Bayesian probability theory, reinforcement learning and efficient coding. I suggest that this theory addresses the general computational problem facing the nervous system. Each neuron is proposed to mirror the function of the whole system in learning to predict aspects of the world related to future reward. According to the model, a typical neuron receives current information about the state of the world from a subset of its excitatory synaptic inputs, and prior information from its other inputs. Prior information would be contributed by synaptic inputs representing distinct regions of space, and by different types of non-synaptic, voltage-regulated channels representing distinct periods of the past. The neuron's membrane voltage is proposed to signal the difference between current and prior information ("prediction error" or "surprise". A neuron would apply a Hebbian plasticity rule to select those excitatory inputs that are the most closely correlated with reward but are the least predictable, since unpredictable inputs provide the neuron with the most "new" information about future reward. To minimize the error in its predictions and to respond only when excitation is "new and surprising," the neuron selects amongst its prior information sources through an anti-Hebbian rule. The unique inputs of a mature neuron would therefore result from learning about spatial and temporal patterns in its local environment, and by extension, the external world. Thus the theory describes how the structure of the mature nervous system could reflect the structure of the external world, and how the complexity and intelligence of the system might develop from a population of

Application of synchrotron radiation for elemental microanalysis of human central nervous system tissue

Energy Technology Data Exchange (ETDEWEB)

Szczerbowska-Boruchowska, M.; Lankosz, M.; Ostachowicz, J. [Mining University, Dept. of Radipmetry, Faculty of Physics and Nuclear Techniques, Krakow (Poland); Adamek, D.; Krygowska-Wajs, A.; Tomik, B.; Szczudlik, A. [Jagiellonian University, Institute of Neurology, Collegium Medicum, Krakow (Poland); Simionovici, A.; Bohic, S. [European Synchrotron Radiation Facility ESRF, 38 - Grenoble (France)

2002-08-01

The pathogenesis of two neuro-degenerative diseases i.e, Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS) are still not known. It is supposed that disturbance of metal ions homeostasis may promote degeneration and atrophy of neurons. As a preliminary study, the quantitative and topographic elemental analysis of selected parts of human brain and spinal cord was performed using synchrotron microbeam-X ray fluorescence ({mu}-SXRF) technique. The samples were taken during the autopsy from patients with PD, ALS and from patients died due to non-neurological conditions events. X-ray fluorescence imaging showed that increased concentration of selected elements are observed in neurons perikaryal parts in compare with surrounding area. Moreover, comparable analysis showed significant differences in accumulation of selected elements between the pathological and control case. The investigations indicate that micro-beam of synchrotron radiation can be satisfactory applied for analysis of central nervous system tissue providing useful information about distribution and contents of elements at the single cell level. (authors)

Optimal size of stochastic Hodgkin-Huxley neuronal systems for maximal energy efficiency in coding pulse signals

Science.gov (United States)

Yu, Lianchun; Liu, Liwei

2014-03-01

The generation and conduction of action potentials (APs) represents a fundamental means of communication in the nervous system and is a metabolically expensive process. In this paper, we investigate the energy efficiency of neural systems in transferring pulse signals with APs. By analytically solving a bistable neuron model that mimics the AP generation with a particle crossing the barrier of a double well, we find the optimal number of ion channels that maximizes the energy efficiency of a neuron. We also investigate the energy efficiency of a neuron population in which the input pulse signals are represented with synchronized spikes and read out with a downstream coincidence detector neuron. We find an optimal number of neurons in neuron population, as well as the number of ion channels in each neuron that maximizes the energy efficiency. The energy efficiency also depends on the characters of the input signals, e.g., the pulse strength and the interpulse intervals. These results are confirmed by computer simulation of the stochastic Hodgkin-Huxley model with a detailed description of the ion channel random gating. We argue that the tradeoff between signal transmission reliability and energy cost may influence the size of the neural systems when energy use is constrained.

A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity.

Directory of Open Access Journals (Sweden)

Romain Cartoni

Full Text Available Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons. Here, using a microfluidic culture system we compared neurons co-deleted for PTEN and SOCS3, an established model of high axonal regeneration capacity, to control neurons. We measured the axonal transport of three cargos (mitochondria, synaptic vesicles and late endosomes in regenerating axons and found that the transport of mitochondria, but not the other cargos, was increased in PTEN/SOCS3 co-deleted axons relative to controls. The results reported here suggest a pivotal role for this organelle during axonal regeneration.

Long-term modulation of the intrinsic cardiac nervous system by spinal cord neurons in normal and ischaemic hearts

NARCIS (Netherlands)

Armour, JA; Linderoth, B; Arora, RC; DeJongste, MJL; Ardell, JL; Kingma, JG; Hill, M; Foreman, RD

2002-01-01

Electrical excitation of the dorsal aspect of the rostral thoracic spinal cord imparts long-term therapeutic benefits to patients with angina pectoris. Such spinal cord stimulation also induces short-term suppressor effects on the intrinsic cardiac nervous system. The purpose of this study was to

The role of amino acids on the development of radiation-induced damage of central nervous system

International Nuclear Information System (INIS)

Yamatodani, Atsushi; Yamamoto, Kouichi; Nohara, Kyoko; Moriyasu, Saeko; Yamamoto, Takashi

2005-01-01

Radiation impairs some functions of the central nervous system, which is one of the radiation-resistant tissues in the body. However, the underlying mechanisms are still unclear. In this study, we investigated the effects of the effects of high-linear energy transfer (LET) heavy-ions on the release of glutamate, the major excitatory neurotransmitter in the central nervous system, in the hypothalamus of rats measured by in vivo brain microdialysis. Total body and head, but not abdominal, heavy-ion (carbon) irradiation induced a significant increase in glutamate levels to approximately 150% of the basal level at 1.5 h of the irradiation, and the release gradually increased during the observation period. Furthermore, heavy-ion-induced glutamate release was suppressed by pretreatment with the dexamethasone. These results suggested that the central pathways (i.e. the neuronal damage of the brain or inflammatory cytokines which were produced in the brain) are involved in the development of high-LET radiation-induced glutamate release. (author)

Anatomical Organization of Urocortin 3-Synthesizing Neurons and Immunoreactive Terminals in the Central Nervous System of Non-Human Primates [Sapajus spp.

Directory of Open Access Journals (Sweden)

Daniella S. Battagello

2017-07-01

Full Text Available Urocortin 3 (UCN3 is a neuropeptide member of the corticotropin-releasing factor (CRF peptide family that acts as a selective endogenous ligand for the CRF, subtype 2 (CRF2 receptor. Immunohistochemistry and in situ hybridization data from rodents revealed UCN3-containing neurons in discrete regions of the central nervous system (CNS, such as the medial preoptic nucleus, the rostral perifornical area (PFA, the medial nucleus of the amygdala and the superior paraolivary nucleus. UCN3-immunoreactive (UCN3-ir terminals are distributed throughout regions that mostly overlap with regions of CRF2 messenger RNA (mRNA expression. Currently, no similar mapping exists for non-human primates. To better understand the role of this neuropeptide, we aimed to study the UCN3 distribution in the brains of New World monkeys of the Sapajus genus. To this end, we analyzed the gene and peptide sequences in these animals and performed immunohistochemistry and in situ hybridization to identify UCN3 synthesis sites and to determine the distribution of UCN3-ir terminals. The sequencing of the Sapajus spp. UCN3-coding gene revealed 88% and 65% identity to the human and rat counterparts, respectively. Additionally, using a probe generated from monkey cDNA and an antiserum raised against human UCN3, we found that labeled cells are mainly located in the hypothalamic and limbic regions. UCN3-ir axons and terminals are primarily distributed in the ventromedial hypothalamic nucleus (VMH and the lateral septal nucleus (LS. Our results demonstrate that UCN3-producing neurons in the CNS of monkeys are phylogenetically conserved compared to those of the rodent brain, that the distribution of fibers agrees with the distribution of CRF2 in other primates and that there is anatomical evidence for the participation of UCN3 in neuroendocrine control in primates.

Activity-Dependent NPAS4 Expression and the Regulation of Gene Programs Underlying Plasticity in the Central Nervous System

Directory of Open Access Journals (Sweden)

José Fernando Maya-Vetencourt

2013-01-01

Full Text Available The capability of the brain to change functionally in response to sensory experience is most active during early stages of development but it decreases later in life when major alterations of neuronal network structures no longer take place in response to experience. This view has been recently challenged by experimental strategies based on the enhancement of environmental stimulation levels, genetic manipulations, and pharmacological treatments, which all have demonstrated that the adult brain retains a degree of plasticity that allows for a rewiring of neuronal circuitries over the entire life course. A hot spot in the field of neuronal plasticity centres on gene programs that underlie plastic phenomena in adulthood. Here, I discuss the role of the recently discovered neuronal-specific and activity-dependent transcription factor NPAS4 as a critical mediator of plasticity in the nervous system. A better understanding of how modifications in the connectivity of neuronal networks occur may shed light on the treatment of pathological conditions such as brain damage or disease in adult life, some of which were once considered untreatable.

Extraversion, Neuroticism and Strength of the Nervous System

Science.gov (United States)

Frigon, Jean-Yves

1976-01-01

The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction…

Central nervous system depressant activityof Leonurus sibiricus ...

African Journals Online (AJOL)

The methanol extract of aerial parts of Leonurus sibiricus was shown to possess central nervous system depressant action by significantly decreased the time of onset of sleep and potentiated the pentobarbital induced sleeping time in mice. Keywords: Leonurus sibiricus, labiatae, central nervous depressant, sedation

Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment

Science.gov (United States)

... teratoid/rhabdoid tumor. There is no standard staging system for central nervous system atypical teratoid/rhabdoid tumor. The extent or spread ... different types of treatment for patients with central nervous system atypical teratoid/rhabdoid tumor. Different types of treatment ...

Nutritional and metabolic diseases involving the nervous system.

Science.gov (United States)

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

Central nervous system affecting drugs and road traffic accidents ...

African Journals Online (AJOL)

Central nervous system affecting drugs and road traffic accidents among commercial motorcyclists. ... including driving under the influence of drugs that affect the central nervous system (CNS). ... Keywords: Brain, influence, riders, substances ...

T-2 mycotoxin treatment of newborn rat pups does not significantly affect nervous system functions in adulthood.

Science.gov (United States)

Varró, Petra; Béldi, Melinda; Kovács, Melinda; Világi, Ildikó

2018-03-01

T-2 toxin is primarily produced by Fusarium sp. abundant under temperate climatic conditions. Its main harmful effect is the inhibition of protein synthesis. Causing oxidative stress, it also promotes lipid peroxidation and changes plasma membrane phospholipid composition; this may lead to nervous system alterations. The aim of the present study was to examine whether a single dose of T-2 toxin administered at newborn age has any long-lasting effects on nervous system functions. Rat pups were treated on the first postnatal day with a single intraperitoneal dose of T-2 toxin (0.2 mg/bwkg). Body weight of treated pups was lower during the second and third week of life, compared to littermates; later, weight gain was recovered. At young adulthood, behavior was tested in the open field, and no difference was observed between treated and control rats. Field potential recordings from somatosensory cortex and hippocampus slices did not reveal any significant difference in neuronal network functions. In case of neocortical field EPSP, the shape was slightly different in treated pups. Long-term synaptic plasticity was also comparable in both groups. Seizure susceptibility of the slices was not different, either. In conclusion, T-2 toxin did not significantly affect basic nervous system functions at this dose.

Hydrogels for central nervous system therapeutic strategies.

Science.gov (United States)

Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

2015-12-01

The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described. © IMechE 2015.

The function of mirror neurons in the learning process

OpenAIRE

Mara Daniel

2017-01-01

In the last years, Neurosciences have developed very much, being elaborated many important theories scientific research in the field. The main goal of neuroscience is to understand how groups of neurons interact to create the behavior. Neuroscientists studying the action of molecules, genes and cells. It also explores the complex interactions involved in motion perception, thoughts, emotions and learning. Brick fundamental nervous system is the nerve cell, neuron. Neurons exchange information...

Cell fate control in the developing central nervous system

Energy Technology Data Exchange (ETDEWEB)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

2014-02-01

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.

Cell fate control in the developing central nervous system

International Nuclear Information System (INIS)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie

2014-01-01

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals

50-57 Effects of the Autonomic Nervous System, Centra

African Journals Online (AJOL)

admin

facilitation of absorption process and expulsion of the undigested food material through ... which is associated with the enteric nervous system , autonomic nervous system and the higher ..... short-chain neutralized fatty acids and 5-HT or radial ...

Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

Directory of Open Access Journals (Sweden)

Yasuhiro Ishihara

2015-01-01

Full Text Available Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury.

The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System.

Science.gov (United States)

Obata, Yuuki; Pachnis, Vassilis

2016-11-01

The gastrointestinal (GI) tract is essential for the absorption of nutrients, induction of mucosal and systemic immune responses, and maintenance of a healthy gut microbiota. Key aspects of gastrointestinal physiology are controlled by the enteric nervous system (ENS), which is composed of neurons and glial cells. The ENS is exposed to and interacts with the outer (microbiota, metabolites, and nutrients) and inner (immune cells and stromal cells) microenvironment of the gut. Although the cellular blueprint of the ENS is mostly in place by birth, the functional maturation of intestinal neural networks is completed within the microenvironment of the postnatal gut, under the influence of gut microbiota and the mucosal immune system. Recent studies have shown the importance of molecular interactions among microbiota, enteric neurons, and immune cells for GI homeostasis. In addition to its role in GI physiology, the ENS has been associated with the pathogenesis of neurodegenerative disorders, such as Parkinson's disease, raising the possibility that microbiota-ENS interactions could offer a viable strategy for influencing the course of brain diseases. Here, we discuss recent advances on the role of microbiota and the immune system on the development and homeostasis of the ENS, a key relay station along the gut-brain axis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Central and peripheral nervous systems: master controllers in cancer metastasis.

Science.gov (United States)

Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

2013-12-01

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

Focal lesions in the central nervous system

International Nuclear Information System (INIS)

Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

1980-01-01

This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

Statin therapy inhibits remyelination in the central nervous system

DEFF Research Database (Denmark)

Miron, Veronique E; Zehntner, Simone P; Kuhlmann, Tanja

2009-01-01

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood...... that OPCs were maintained in an immature state (Olig2(strong)/Nkx2.2(weak)). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating...... the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes....

Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system.

Science.gov (United States)

Ivanova, Anna; Wuerfel, Jens; Zhang, Juan; Hoffmann, Olaf; Ballmaier, Matthias; Dame, Christof

2010-07-28

Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI. Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain. Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

Laser puncture therapy of nervous system disorders

Energy Technology Data Exchange (ETDEWEB)

Anishchenko, G.; Kochetkov, V.

1984-08-29

The authors discuss experience with treatment of nervous system disorders by means of laser-puncture therapy. Commenting on the background of the selection of this type of treatment, they explain that once researchers determined the biological action of laser light on specific nerve receptors of the skin, development of laser apparatus capable of concentrating the beam in the millimeter band was undertaken. The devices that are being used for laser-puncture are said to operate in the red helium-neon band of light. The authors identify beam parameters that have been selected for different groups of acupuncture points of the skin, and the courses of treatment (in seconds of radiation) and their time intervals. They go on to discuss the results of treatment of over 800 patients categorized in a group with disorders of the peripheral nervous system and a second group with disorders of the central nervous system.

Structural and functional features of central nervous system lymphatic vessels.

Science.gov (United States)

Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

2015-07-16

One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

Central Nervous System Infections in Denmark

Science.gov (United States)

2018-02-04

Central Nervous System Infections; Bacterial Meningitis; Viral Meningitis; Aseptic Meningitis; Encephalitis; Brain Abscess; Neuroborreliosis; Neurosyphilis; Lyme Disease; Tertiary Syphilis; Cerebral Abscess; Meningitis

Glial Cells: The Other Cells of the Nervous System

Indian Academy of Sciences (India)

nervous system. The present .... In the vertebrate nervous system, special types of cells called radial glia .... As men- tioned earlier, astrocytes extend a 'foot process' (Figure 3) that ... capillaries that for a long time it was thought that these cells.

The Nervous System Game

Science.gov (United States)

Corbitt, Cynthia; Carpenter, Molly

2006-01-01

For many children, especially those with reading difficulties, a motor-kinesthetic learning activity may be an effective tool to teach complex concepts. With this in mind, the authors developed and tested a game designed to teach fourth- to sixth-grade children some basic principles of nervous system function by allowing the children themselves to…

Runx transcription factors in neuronal development

Directory of Open Access Journals (Sweden)

Shiga Takashi

2008-08-01

Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

Explanation of diagnostic criteria for radiation-induced nervous system disease

International Nuclear Information System (INIS)

Xing Zhiwei; Jiang Enhai

2012-01-01

National occupational health standard-Diagnostic Criteria for Radiation-Induced Nervous System Disease has been issued and implemented by the Ministry of health. This standard contained three independent criteria of the brain, spinal cord and peripheral nerve injury. These three kinds of disease often go together in clinic,therefore,the three diagnostic criteria were merged into radioactive nervous system disease diagnostic criteria for entirety and maneuverability of the standard. This standard was formulated based on collection of the clinical practice experience, extensive research of relevant literature and foreign relevant publications. It is mainly applied to diagnosis and treatment of occupational radiation-induced nervous system diseases, and to nervous system diseases caused by medical radiation exposure as well. In order to properly implement this standard, also to correctly deal with radioactive nervous system injury, the main contents of this standard including dose threshold, clinical manifestation, indexing standard and treatment principle were interpreted in this article. (authors)

Microbiota-gut-brain axis and the central nervous system

OpenAIRE

Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

2017-01-01

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated ...

Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

Science.gov (United States)

Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

2015-01-01

Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments

Advanced in study of cellular and molecular mechanisms of radiation effects on central nervous system

International Nuclear Information System (INIS)

Zhang Wei; Tu Yu; Wang Lili

2008-01-01

Along with radiation treatment extensively applied, radiation injury also is valued gradually. The effect of radiation to the cellular and molecular of central nervous system (CNS) is a complicated and moderately advanced process and the mechanism is remains incompletely clear yet. Inquiring into the possible mechanism of the CNS including the injury and the restoration of neuron, neuroglia cells, endotheliocyte cell and blood-brain barrier and the molecular level of change induced by radiation, so as to provide beneficial thought for preventing and curing radiation injury clinically. Some neuroprotective strategies are also addressed in the review. (authors)

NEUROSPECIFIC ENOLASE IN DIAGNOSTICS FOR PERINATAL DAMAGE TO THE CENTRAL NERVOUS SYSTEM IN PREMATURE INFANTS

Directory of Open Access Journals (Sweden)

E.G. Novopol'tseva

2010-01-01

Full Text Available Neurospecific enolase is an endoenzyme of the central nervous system (CNS present in neurons of the brain and peripheral neuraltissue. This is currently the only known general marker of all differentiated neurons. The article illustrates the results of determining this enzyme in premature infants with fetal infections and assessment of their importance as a marker of damage to CNS in this group of children. A high level of neurospecific enolase in children with infectious and inflammatory diseases is not only the marker of damage to blood-brain barrier, but also reflects the nature of damage (hypoxia, intoxication, inflammation. This parameter in premature infants with various pathologies may serve as a degree of perinatal damage severity, and along with other parameters, determine the performed therapy tactics. Key words: neurospecific enolase, marker of CNS damage, perinatal damage, children. (Pediatric Pharmacology. – 2010; 7(3:66-70

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

Science.gov (United States)

Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

2015-05-19

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

Pharmacotherapy for Adults with Tumors of the Central Nervous System

OpenAIRE

Schor, Nina F.

2008-01-01

Tumors of the adult central nervous system are among the most common and most chemoresistant neoplasms. Malignant tumors of the brain and spinal cord collectively account for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the current approaches and challenges to successful pharmacotherapy of adults with malignant tumors of the central nervous system and discusses novel...

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

Science.gov (United States)

2016-10-01

AWARD NUMBER: W81XWH-14-1-0586 TITLE: Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring PRINCIPAL...Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring 5a. CONTRACT NUMBER W81XWH-14-1-0586 5b. GRANT NUMBER W81XWH- 14-1-0586 5c...barriers that prevent the optimal delivery of biologics and cells to the injured nervous system . A significant problem is the formation of scar tissue

Localization of rem2 in the central nervous system of the adult rainbow trout (Oncorhynchus mykiss).

Science.gov (United States)

Downs, Anna G; Scholles, Katie R; Hollis, David M

2016-12-01

Rem2 is member of the RGK (Rem, Rad, and Gem/Kir) subfamily of the Ras superfamily of GTP binding proteins known to influence Ca 2+ entry into the cell. In addition, Rem2, which is found at high levels in the vertebrate brain, is also implicated in cell proliferation and synapse formation. Though the specific, regional localization of Rem2 in the adult mammalian central nervous system has been well-described, such information is lacking in other vertebrates. Rem2 is involved in neuronal processes where the capacities between adults of different vertebrate classes vary. Thus, we sought to localize the rem2 gene in the central nervous system of an adult anamniotic vertebrate, the rainbow trout (Oncorhynchus mykiss). In situ hybridization using a digoxigenin (DIG)-labeled RNA probe was used to identify the regional distribution of rem2 expression throughout the trout central nervous system, while real-time polymerase chain reaction (rtPCR) further supported these findings. Based on in situ hybridization, the regional distribution of rem2 occurred within each major subdivision of the brain and included large populations of rem2 expressing cells in the dorsal telencephalon of the cerebrum, the internal cellular layer of the olfactory bulb, and the optic tectum of the midbrain. In contrast, no rem2 expressing cells were resolved within the cerebellum. These results were corroborated by rtPCR, where differential rem2 expression occurred between the major subdivisions assayed with the highest levels being found in the cerebrum, while it was nearly absent in the cerebellum. These data indicate that rem2 gene expression is broadly distributed and likely influences diverse functions in the adult fish central nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

Science.gov (United States)

Gordon, Tessa; Gordon, Karen

2010-01-01

Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

Interferons in the central nervous system

DEFF Research Database (Denmark)

Owens, Trevor; Khorooshi, Reza M. H.; Wlodarczyk, Agnieszka

2014-01-01

Interferons (IFNs) are implicated as an important component of the innate immune system influencing viral infections, inflammation, and immune surveillance. We review here the complex biological activity of IFNs in the central nervous system (CNS) and associated glial–immune interactions...

Spatial distribution of cannabinoid receptor type 1 (CB1 in normal canine central and peripheral nervous system.

Directory of Open Access Journals (Sweden)

Jessica Freundt-Revilla

Full Text Available The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2 and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

Life and understanding:the origins of ‘understanding’ in self-organizing nervous systems.

Directory of Open Access Journals (Sweden)

Yan Mark Yufik

2016-12-01

Full Text Available This article is motivated by the formulation of biotic self-organisation in (Friston, 2013, where the emergence of ‘life’ in coupled material entities (e.g., macromolecules was predicated on bounded subsets that maintain a degree of statistical independence from the rest of the network. Boundary elements in such systems or units constitute a Markov blanket; separating the internal states of the unit from its surrounding states. In this paper, we ask whether Markov blankets operate in the nervous system and underlie the development of intelligence, enabling a progression from the ability to sense the environment to the ability to understand it. Markov blankets have been previously hypothesized to form in neuronal networks as a result of phase transitions that cause network subsets to fold into bounded assemblies, or packets (Yufik, 1998a. The ensuing neuronal packets hypothesis builds on the notion of neuronal assemblies (Hebb, 1949, 1980, treating such assemblies as flexible but stable biophysical structures capable of withstanding entropic erosion. In other words, structures that maintain their integrity under changing conditions. In this treatment, neuronal packets give rise to perception of ’objects’; i.e., quasi-stable (stimulus bound groupings that are conserved over multiple presentations (e.g., the experience of perceiving ‘apple’ can be interrupted and resumed many times. Monitoring the variations in such groups enables the apprehension of behaviour; i.e., attributing to objects the ability to undergo changes without loss of self-identity. Ultimately, ‘understanding’ involves self-directed composition and manipulation of the ensuing ‘mental models’ that are constituted by neuronal packets, whose dynamics capture relationships among objects: that is, dependencies in the behaviour of objects under varying conditions. For example, movement is known to involve rotation of population vectors in the motor cortex

Sjogrens Syndrome Presenting with Central Nervous System Involvement

Directory of Open Access Journals (Sweden)

Tülay Terzi

2012-01-01

Full Text Available Sjogren’s syndrome is a slowly progressive autoimmune disease. Neurological involvement occurs in approximately 20-25% cases in Sjogren’s syndrome. 87% of the neurological involvement is peripheral nervous system, almost 13% in the form of central nervous system involvement. Affected central nervous system may show similar clinical and radiological findings as in multiple sclerosis (MS. In this paper, a 43-year-old patient is discussed who was referred with the complaint of dizziness, there was MS- like lesions in brain imaging studies and was diagnosed with Sjogren’s syndrome. MS- like clinical and radiologic tables can be seen, albeit rarely in Sjogren’s syndrome. In these cases, early diagnosis and early treatment for the sjögren has a great importance for the prognosis of the disease.

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Nakadai, Taeko; Khono, Yukio; Nagaoka, Shunji

2004-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using mouse neonatal brain cells in culture exposed to heavy ions and X ray at fifth days of the culture. The subsequent biological effects were evaluated by an induction of apoptosis and the survivability of neurons focusing on the dependencies of the animal strains with different genetic types, and linear energy transfer (LET) of the different nucleons. Of the three mouse strains tested, SCID, B6, B6C3F1 and C3H, used for brain cell culture, SCID was the most sensitive. Radiation sensitivity of these cells ware SCID>B6>B6C3F1>C3H to both X-ray and carbon ion (290 MeV/n) when compared by 10% apoptotic induction. The LET dependency was compared with using SCID cells exposing to different ions, (X, C, Si, Ar, and Fe). Although no detectable LET dependency was observed at higher dose than 1 Gy, an enhancement was observed in the high LET region and at lower dose than 0.5 Gy. The survivability profiles of the neurons were different in the mouse strains and ions. Memory and learning function of adult mice were studied using water maze test after localized carbon- or iron-ion irradiation to hippocampus area. Memory function were rapidly decrease after irradiation both ions. C-ion group were recovered 20 weeks after irradiation, but Iron group were different. (author)

A distance constrained synaptic plasticity model of C. elegans neuronal network

Science.gov (United States)

Badhwar, Rahul; Bagler, Ganesh

2017-03-01

Brain research has been driven by enquiry for principles of brain structure organization and its control mechanisms. The neuronal wiring map of C. elegans, the only complete connectome available till date, presents an incredible opportunity to learn basic governing principles that drive structure and function of its neuronal architecture. Despite its apparently simple nervous system, C. elegans is known to possess complex functions. The nervous system forms an important underlying framework which specifies phenotypic features associated to sensation, movement, conditioning and memory. In this study, with the help of graph theoretical models, we investigated the C. elegans neuronal network to identify network features that are critical for its control. The 'driver neurons' are associated with important biological functions such as reproduction, signalling processes and anatomical structural development. We created 1D and 2D network models of C. elegans neuronal system to probe the role of features that confer controllability and small world nature. The simple 1D ring model is critically poised for the number of feed forward motifs, neuronal clustering and characteristic path-length in response to synaptic rewiring, indicating optimal rewiring. Using empirically observed distance constraint in the neuronal network as a guiding principle, we created a distance constrained synaptic plasticity model that simultaneously explains small world nature, saturation of feed forward motifs as well as observed number of driver neurons. The distance constrained model suggests optimum long distance synaptic connections as a key feature specifying control of the network.

Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System

Directory of Open Access Journals (Sweden)

Marleen eVan Coevorden-Hameete

2016-05-01

Full Text Available Autoimmune encephalitis (AIE is a group of disorders in which autoantibodies directed at antigens located on the plasma membrane of neurons induce severe neurological symptoms. In contrast to classical paraneoplastic disorders, AIE patients respond well to immunotherapy. The detection of neuronal surface autoantibodies in patients’ serum or CSF therefore has serious consequences for the patients’ treatment and follow-up and requires the availability of sensitive and specific diagnostic tests. This mini-review provides a guideline for both diagnostic and research laboratories that work on the detection of known surface autoantibodies and/or the identification of novel surface antigens. We discuss the strengths and pitfalls of different techniques for anti-neuronal antibody detection: 1 Immunohistochemistry and immunofluorescence on rat/ primate brain sections, 2 Immunocytochemistry of living cultured hippocampal neurons, 3 Cell Based Assay (CBA. In addition, we discuss the use of immunoprecipitation and mass spectrometry analysis for the detection of novel neuronal surface antigens, which is a crucial step in further disease classification and the development of novel CBAs.

Life and Understanding: The Origins of "Understanding" in Self-Organizing Nervous Systems.

Science.gov (United States)

Yufik, Yan M; Friston, Karl

2016-01-01

This article is motivated by a formulation of biotic self-organization in Friston (2013), where the emergence of "life" in coupled material entities (e.g., macromolecules) was predicated on bounded subsets that maintain a degree of statistical independence from the rest of the network. Boundary elements in such systems constitute a Markov blanket ; separating the internal states of a system from its surrounding states. In this article, we ask whether Markov blankets operate in the nervous system and underlie the development of intelligence, enabling a progression from the ability to sense the environment to the ability to understand it. Markov blankets have been previously hypothesized to form in neuronal networks as a result of phase transitions that cause network subsets to fold into bounded assemblies, or packets (Yufik and Sheridan, 1997; Yufik, 1998a). The ensuing neuronal packets hypothesis builds on the notion of neuronal assemblies (Hebb, 1949, 1980), treating such assemblies as flexible but stable biophysical structures capable of withstanding entropic erosion. In other words, structures that maintain their integrity under changing conditions. In this treatment, neuronal packets give rise to perception of "objects"; i.e., quasi-stable (stimulus bound) feature groupings that are conserved over multiple presentations (e.g., the experience of perceiving "apple" can be interrupted and resumed many times). Monitoring the variations in such groups enables the apprehension of behavior; i.e., attributing to objects the ability to undergo changes without loss of self-identity. Ultimately, "understanding" involves self-directed composition and manipulation of the ensuing "mental models" that are constituted by neuronal packets, whose dynamics capture relationships among objects: that is, dependencies in the behavior of objects under varying conditions. For example, movement is known to involve rotation of population vectors in the motor cortex (Georgopoulos et al

Intrinsic neuromodulation: altering neuronal circuits from within.

Science.gov (United States)

Katz, P S; Frost, W N

1996-02-01

There are two sources of neuromodulation for neuronal circuits: extrinsic inputs and intrinsic components of the circuits themselves. Extrinsic neuromodulation is known to be pervasive in nervous systems, but intrinsic neuromodulation is less recognized, despite the fact that it has now been demonstrated in sensory and neuromuscular circuits and in central pattern generators. By its nature, intrinsic neuromodulation produces local changes in neuronal computation, whereas extrinsic neuromodulation can cause global changes, often affecting many circuits simultaneously. Studies in a number of systems are defining the different properties of these two forms of neuromodulation.

Vitamin D and the central nervous system.

Science.gov (United States)

Wrzosek, Małgorzata; Łukaszkiewicz, Jacek; Wrzosek, Michał; Jakubczyk, Andrzej; Matsumoto, Halina; Piątkiewicz, Paweł; Radziwoń-Zaleska, Maria; Wojnar, Marcin; Nowicka, Grażyna

2013-01-01

Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

Functional properties of human neuronal Kv11 channels

DEFF Research Database (Denmark)

Einarsen, Karoline; Calloe, Kirstine; Grunnet, Morten

2009-01-01

Kv11 potassium channels are important for regulation of the membrane potential. Kv11.2 and Kv11.3 are primarily found in the nervous system, where they most likely are involved in the regulation of neuronal excitability. Two isoforms of human Kv11.2 have been published so far. Here, we present...... current characteristics of the isoforms presented in this work may contribute to the regulation of neuronal excitability....

Cellular Links between Neuronal Activity and Energy Homeostasis

OpenAIRE

Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

2012-01-01

Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which lea...

The nervous systems of basally branching nemertea (palaeonemertea.

Directory of Open Access Journals (Sweden)

Patrick Beckers

Full Text Available In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

Morphological evidence for novel enteric neuronal circuitry in guinea pig distal colon.

Science.gov (United States)

Smolilo, D J; Costa, M; Hibberd, T J; Wattchow, D A; Spencer, Nick J

2018-07-01

The gastrointestinal (GI) tract is unique compared to all other internal organs; it is the only organ with its own nervous system and its own population of intrinsic sensory neurons, known as intrinsic primary afferent neurons (IPANs). How these IPANs form neuronal circuits with other functional classes of neurons in the enteric nervous system (ENS) is incompletely understood. We used a combination of light microscopy, immunohistochemistry and confocal microscopy to examine the topographical distribution of specific classes of neurons in the myenteric plexus of guinea-pig colon, including putative IPANs, with other classes of enteric neurons. These findings were based on immunoreactivity to the neuronal markers, calbindin, calretinin and nitric oxide synthase. We then correlated the varicose outputs formed by putative IPANs with subclasses of excitatory interneurons and motor neurons. We revealed that calbindin-immunoreactive varicosities form specialized structures resembling 'baskets' within the majority of myenteric ganglia, which were arranged in clusters around calretinin-immunoreactive neurons. These calbindin baskets directly arose from projections of putative IPANs and represent morphological evidence of preferential input from sensory neurons directly to a select group of calretinin neurons. Our findings uncovered that these neurons are likely to be ascending excitatory interneurons and excitatory motor neurons. Our study reveals for the first time in the colon, a novel enteric neural circuit, whereby calbindin-immunoreactive putative sensory neurons form specialized varicose structures that likely direct synaptic outputs to excitatory interneurons and motor neurons. This circuit likely forms the basis of polarized neuronal pathways underlying motility. © 2018 Wiley Periodicals, Inc.

Designing and implementing nervous system simulations on LEGO robots.

Science.gov (United States)

Blustein, Daniel; Rosenthal, Nikolai; Ayers, Joseph

2013-05-25

We present a method to use the commercially available LEGO Mindstorms NXT robotics platform to test systems level neuroscience hypotheses. The first step of the method is to develop a nervous system simulation of specific reflexive behaviors of an appropriate model organism; here we use the American Lobster. Exteroceptive reflexes mediated by decussating (crossing) neural connections can explain an animal's taxis towards or away from a stimulus as described by Braitenberg and are particularly well suited for investigation using the NXT platform.(1) The nervous system simulation is programmed using LabVIEW software on the LEGO Mindstorms platform. Once the nervous system is tuned properly, behavioral experiments are run on the robot and on the animal under identical environmental conditions. By controlling the sensory milieu experienced by the specimens, differences in behavioral outputs can be observed. These differences may point to specific deficiencies in the nervous system model and serve to inform the iteration of the model for the particular behavior under study. This method allows for the experimental manipulation of electronic nervous systems and serves as a way to explore neuroscience hypotheses specifically regarding the neurophysiological basis of simple innate reflexive behaviors. The LEGO Mindstorms NXT kit provides an affordable and efficient platform on which to test preliminary biomimetic robot control schemes. The approach is also well suited for the high school classroom to serve as the foundation for a hands-on inquiry-based biorobotics curriculum.

CT diagnosis of congenital anomalies of the central nervous system

International Nuclear Information System (INIS)

Mori, Koreaki

1980-01-01

In the diagnosis of central nervous system congenital anomalies, understanding of embryology of the central nervous system and pathophysiology of each anomaly are essential. It is important for clinical approach to central nervous system congenital anomalies to evaluate the size of the head and tention of the anterior fontanelle. Accurate diagnosis of congenital anomalies depends on a correlation of CT findings to clinical pictures. Clinical diagnosis of congenital anomalies should include prediction of treatability and prognosis, in addition to recognition of a disease. (author)

Divergent and convergent roles for insulin-like peptides in the worm, fly and mammalian nervous systems.

Science.gov (United States)

Lau, Hiu E; Chalasani, Sreekanth H

2014-09-01

Insulin signaling plays a critical role in coupling external changes to animal physiology and behavior. Despite remarkable conservation in the insulin signaling pathway components across species, divergence in the mechanism and function of the signal is evident. Focusing on recent findings from C. elegans, D. melanogaster and mammals, we discuss the role of insulin signaling in regulating adult neuronal function and behavior. In particular, we describe the transcription-dependent and transcription-independent aspects of insulin signaling across these three species. Interestingly, we find evidence of diverse mechanisms underlying complex networks of peptide action in modulating nervous system function.

APPLICATION OF UKRAINIAN GRID INFRASTRUCTURE FOR INVESTIGATION OF NONLINEAR DYNAMICS IN LARGE NEURONAL NETWORKS

Directory of Open Access Journals (Sweden)

O. О. Sudakov

2015-12-01

Full Text Available In present work the Ukrainian National Grid (UNG infrastructure was applied for investigation of synchronization in large networks of interacting neurons. This application is important for solving of modern neuroscience problems related to mechanisms of nervous system activities (memory, cognition etc. and nervous pathologies (epilepsy, Parkinsonism, etc.. Modern non-linear dynamics theories and applications provides powerful basis for computer simulations of biological neuronal networks and investigation of phenomena which mechanisms hardly could be clarified by other approaches. Cubic millimeter of brain tissue contains about 105 neurons, so realistic (Hodgkin-Huxley model and phenomenological (Kuramoto-Sakaguchi, FitzHugh-Nagumo, etc. models simulations require consideration of large neurons numbers.

Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

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Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

2007-03-01

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

MIRNAS in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity

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Carlos Lafourcade

2016-01-01

Full Text Available Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate in multivesicular bodies of parent cells and are secreted by fusion of the multivesicular body limiting membrane with the plasma membrane. Their molecular cargo, consisting of RNA species, proteins, and lipids, is in part cell type and cell state specific. Among the RNA species transported by exosomes, microRNAs (miRNAs are able to modify gene expression in recipient cells. Several miRNAs present in astrocytes are regulated under pathological conditions, and this may have far-reaching consequences if they are loaded in exosomes. We propose that astrocyte-derived miRNA-loaded exosomes, such as miR-26a, are dysregulated in several central nervous system diseases; thus potentially controlling neuronal morphology and synaptic transmission through validated and predicted targets. Unraveling the contribution of this new signaling mechanism to the maintenance and plasticity of neuronal networks will impact our understanding on the physiology and pathophysiology of the central nervous system.

Conductive polymers for controlled release and treatment of central nervous system injury

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Saigal, Rajiv

As one of the most devastating forms of neurotrauma, spinal cord injury remains a challenging clinical problem. The difficulties in treatment could potentially be resolved by better technologies for therapeutic delivery. In order to develop new approaches to treating central nervous system injury, this dissertation focused on using electrically-conductive polymers, controlled drug release, and stem cell transplantation. We first sought to enhance the therapeutic potential of neural stem cells by electrically increasing their production of neurotrophic factors (NTFs), important molecules for neuronal cell survival, differentiation, synaptic development, plasticity, and growth. We fabricated a new cell culture device for growing neural stem cells on a biocompatible, conductive polymer. Electrical stimulation via the polymer led to upregulation of NTF production by neural stem cells. This approach has the potential to enhance stem cell function while avoiding the pitfalls of genetic manipulation, possibly making stem cells more viable as a clinical therapy. Seeing the therapeutic potential of conductive polymers, we extended our studies to an in vivo model of spinal cord injury (SCI). Using a novel fabrication and extraction technique, a conductive polymer was fabricated to fit to the characteristic pathology that follows contusive SCI. Assessed via quantitative analysis of MR images, the conductive polymer significantly reduced compression of the injured spinal cord. Further characterizing astroglial and neuronal response of injured host tissue, we found significant neuronal sparing as a result of this treatment. The in vivo studies also demonstrated improved locomotor recovery mediated by a conductive polymer scaffold over a non-conductive control. We next sought to take advantage of conductive polymers for local, electronically-controlled release of drugs. Seeking to overcome reported limitations in drug delivery via polypyrrole, we first embedded drugs in poly

The mirror neuron system.

Science.gov (United States)

Cattaneo, Luigi; Rizzolatti, Giacomo

2009-05-01

Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

Science.gov (United States)

Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

Radiation induced effects in the developing central nervous system; Effectos radioinducidos sobre el sistema nervioso central en desarrollo

Energy Technology Data Exchange (ETDEWEB)

Gisone, P; Dubner, D; Michelin, S C; Perez, M.R. Del [Autoridad Regulatoria Nuclear, Gerencia de Apoyo Cientifico, Buenos Aires (Argentina)

1997-11-01

The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed. 8 refs.

Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

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Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

2017-09-01

Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

Models of the stochastic activity of neurones

CERN Document Server

Holden, Arun Vivian

1976-01-01

These notes have grown from a series of seminars given at Leeds between 1972 and 1975. They represent an attempt to gather together the different kinds of model which have been proposed to account for the stochastic activity of neurones, and to provide an introduction to this area of mathematical biology. A striking feature of the electrical activity of the nervous system is that it appears stochastic: this is apparent at all levels of recording, ranging from intracellular recordings to the electroencephalogram. The chapters start with fluctuations in membrane potential, proceed through single unit and synaptic activity and end with the behaviour of large aggregates of neurones: L have chgaen this seque~~e\\/~~';uggest that the interesting behaviourr~f :the nervous system - its individuality, variability and dynamic forms - may in part result from the stochastic behaviour of its components. I would like to thank Dr. Julio Rubio for reading and commenting on the drafts, Mrs. Doris Beighton for producing the fin...

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

International Nuclear Information System (INIS)

Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

2011-01-01

Highlights: → Toxicological implications associated with the use of NaNO 2 therapy to treat systemic cell-free Hb exposure are not well-defined. → Systemic Hb exposure followed by NaNO 2 infusion induces acute CNS toxicities in guinea pigs. → These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO 2 alone. → NaNO 2 -mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO 2 ) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO 2 with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO 2 on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO 2 , at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO 2 alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors

DEFF Research Database (Denmark)

von Deimling, A; Fimmers, R; Schmidt, M C

2000-01-01

Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However......, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2...... may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors....

Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE

DEFF Research Database (Denmark)

Liu, Yawei; Teige, Ingrid; Birnir, Bryndis

2006-01-01

Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflamma......Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS......) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1-TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between...... neurons and T cells results in the conversion of encephalitogenic T cells to CD25+ TGF-beta1+ CTLA-4+ FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4...

hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

Science.gov (United States)

Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

2002-08-23

The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

The mirror-neuron system.

Science.gov (United States)

Rizzolatti, Giacomo; Craighero, Laila

2004-01-01

A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.

Chemokines and chemokine receptors in inflammation of the nervous system

DEFF Research Database (Denmark)

Huang, D; Han, Yong-Chang; Rani, M R

2000-01-01

This article focuses on the production of chemokines by resident glial cells of the nervous system. We describe studies in two distinct categories of inflammation within the nervous system: immune-mediated inflammation as seen in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis...

DNA methylation-based classification of central nervous system tumours

DEFF Research Database (Denmark)

Capper, David; Jones, David T.W.; Sill, Martin

2018-01-01

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variabil......Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter......-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show...

Detection of Ca2+-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin

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Tigran R Petrosyan

2016-01-01

Full Text Available The study aims to confirm the neuroregenerative effects of bacterial melanin (BM on central nervous system injury using a special staining method based on the detection of Ca2+-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I; n = 12 or unilateral rubrospinal tract transection at the cervical level (C3–4 (group II; n = 12. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup and the remaining six rats were intramuscularly injected with saline (saline subgroup. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca2+-dependent acid phosphatase activity detection in combination with Chilingarian's calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca2+-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.

Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and Regenerating Nervous Systems

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Felix L. Struebing

2017-11-01

Full Text Available In both the central nervous system (CNS and the peripheral nervous system (PNS, axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin Bdnf and the transcription factor Sox11. Although both molecules act to facilitate successful axon regeneration in the PNS, this process does not occur in the CNS. The present study examines the differential expression of Sox11 and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at different time points: (i the acutely injured CNS (retina after optic nerve crush and PNS (dorsal root ganglion after sciatic nerve crush, (ii a CNS regeneration model (retina after optic nerve crush and induced regeneration; and (iii the retina during a chronic form of central neurodegeneration (the DBA/2J glaucoma model. We find an initial increase of Sox11 in both PNS and CNS after injury; however, the expression of Bdnf isoforms is higher in the PNS relative to the CNS. Sustained upregulation of Sox11 is seen in the injured retina following regeneration treatment, while the expression of two Bdnf mRNA isoforms is suppressed. Furthermore, two isoforms of Sox11 with different 3′UTR lengths are present in the retina, and the long isoform is specifically upregulated in later stages of glaucoma. These results provide insight into the molecular cascades active during axonal injury and regeneration in mammalian neurons.

Microbiota-gut-brain axis and the central nervous system.

Science.gov (United States)

Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

2017-08-08

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

Karolinska Institutet 200-Year Anniversary. Symposium on Traumatic Injuries in the Nervous System: Injuries to the Spinal Cord and Peripheral Nervous System – Injuries and Repair, Pain Problems, Lesions to Brachial Plexus

Science.gov (United States)

Sköld, Mattias K.; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

The role of TAM family receptors and ligands in the nervous system: From development to pathobiology.

Science.gov (United States)

Shafit-Zagardo, Bridget; Gruber, Ross C; DuBois, Juwen C

2018-03-04

Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K-dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 -/- and TAM mutant mice models. Copyright © 2018. Published by Elsevier Inc.

Radiation therapy of tumours of the central nervous system

International Nuclear Information System (INIS)

Skolyszewski, J.

1980-01-01

The aim of this work is to present the principles of radiation therapy of tumours of the central nervous system, according to the experience of the Institute of Oncology in Krakow. The text was designed primarily for the radiotherapists involved in the treatment of tumours of the central nervous system, and may be used as an auxiliary textbook for those preparing for the examination in radiotherapy. (author)

Mutations in the nervous system–specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II

Science.gov (United States)

Shekarabi, Masoud; Girard, Nathalie; Rivière, Jean-Baptiste; Dion, Patrick; Houle, Martin; Toulouse, André; Lafrenière, Ronald G.; Vercauteren, Freya; Hince, Pascale; Laganiere, Janet; Rochefort, Daniel; Faivre, Laurence; Samuels, Mark; Rouleau, Guy A.

2008-01-01

Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system–specific exon of the with-no-lysine(K)–1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII. PMID:18521183

Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

International Nuclear Information System (INIS)

Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

1988-01-01

The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[ 3 H]glucose convert this glucose analogue to 2-deoxy[ 3 H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O 2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system

Honeybee Retinal Glial Cells Transform Glucose and Supply the Neurons with Metabolic Substrate

Science.gov (United States)

Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

1988-11-01

The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system.

Morphological analysis of Drosophila larval peripheral sensory neuron dendrites and axons using genetic mosaics.

Science.gov (United States)

Karim, M Rezaul; Moore, Adrian W

2011-11-07

Nervous system development requires the correct specification of neuron position and identity, followed by accurate neuron class-specific dendritic development and axonal wiring. Recently the dendritic arborization (DA) sensory neurons of the Drosophila larval peripheral nervous system (PNS) have become powerful genetic models in which to elucidate both general and class-specific mechanisms of neuron differentiation. There are four main DA neuron classes (I-IV)(1). They are named in order of increasing dendrite arbor complexity, and have class-specific differences in the genetic control of their differentiation(2-10). The DA sensory system is a practical model to investigate the molecular mechanisms behind the control of dendritic morphology(11-13) because: 1) it can take advantage of the powerful genetic tools available in the fruit fly, 2) the DA neuron dendrite arbor spreads out in only 2 dimensions beneath an optically clear larval cuticle making it easy to visualize with high resolution in vivo, 3) the class-specific diversity in dendritic morphology facilitates a comparative analysis to find key elements controlling the formation of simple vs. highly branched dendritic trees, and 4) dendritic arbor stereotypical shapes of different DA neurons facilitate morphometric statistical analyses. DA neuron activity modifies the output of a larval locomotion central pattern generator(14-16). The different DA neuron classes have distinct sensory modalities, and their activation elicits different behavioral responses(14,16-20). Furthermore different classes send axonal projections stereotypically into the Drosophila larval central nervous system in the ventral nerve cord (VNC)(21). These projections terminate with topographic representations of both DA neuron sensory modality and the position in the body wall of the dendritic field(7,22,23). Hence examination of DA axonal projections can be used to elucidate mechanisms underlying topographic mapping(7,22,23), as well as

A family of splice variants of CstF-64 expressed in vertebrate nervous systems

Science.gov (United States)

Shankarling, Ganesh S; Coates, Penelope W; Dass, Brinda; MacDonald, Clinton C

2009-01-01

expression throughout development. Finally, experiments in representative cell lines suggest that βCstF-64 is expressed in neurons but not glia. Conclusion This is the first report of a family of splice variants encoding a key polyadenylation protein that is expressed in a nervous system-specific manner. We propose that βCstF-64 contributes to proteomic diversity by regulating alternative polyadenylation of neural mRNAs. PMID:19284619

Pazopanib efficacy in recurrent central nervous system hemangiopericytomas.

Science.gov (United States)

Apra, Caroline; Alentorn, Agusti; Mokhtari, Karima; Kalamarides, Michel; Sanson, Marc

2018-04-26

There is currently no treatment for solitary fibrous tumors/hemangiopericytomas (SFT/H) of the central nervous system recurring after multiple surgeries and radiotherapies. The NAB2-STAT6 gene fusion is the hallmark of these tumors, and upregulates Early Growth Factor, activating several growth pathways. We treated two patients presenting pluri-recurrent meningeal SFT/H with Pazopanib, a broad-spectrum tyrosine kinase inhibitor. We analyzed the exome and RNA sequencing data of one of them and, in addition to another meningeal SFT/H, compared it to the transcriptomic profiling of 5 systemic SFT/H. A dramatic clinical and radiological response was observed in both cases, respectively 84 and 43% decrease after 3 months. As a comparison, Pazopanib has only a stabilizing effect in systemic SFT/H. Indeed, central nervous system SFT/H show overexpression of different tyrosine kinases targeted by Pazopanib. Two consecutive patients with untreatable central nervous system SFT/H showed a spectacular partial response to Pazopanib, an unprecedented result in SFT/H. This result could be explained by differences in expression profiles and calls for a confirmation in a larger cohort of patients.

Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass

Science.gov (United States)

Teichert, Russell W.; Memon, Tosifa; Aman, Joseph W.; Olivera, Baldomero M.

2014-01-01

Change is intrinsic to nervous systems; change is required for learning and conditioning and occurs with disease progression, normal development, and aging. To better understand mammalian nervous systems and effectively treat nervous-system disorders, it is essential to track changes in relevant individual neurons. A critical challenge is to identify and characterize the specific cell types involved and the molecular-level changes that occur in each. Using an experimental strategy called constellation pharmacology, we demonstrate that we can define a specific somatosensory neuronal subclass, cold thermosensors, across different species and track changes in these neurons as a function of development. Cold thermosensors are uniformly responsive to menthol and innocuous cool temperature (17 °C), indicating that they express TRPM8 channels. A subset of cold thermosensors expressed α7 nicotinic acetylcholine receptors (nAChRs) but not other nAChR subtypes. Differences in temperature threshold of cold thermosensors correlated with functional expression of voltage-gated K channels Kv1.1/1.2: Relatively higher expression of KV1.1/1.2 channels resulted in a higher threshold response to cold temperature. Other signaling components varied during development and between species. In cold thermosensors of neonatal mice and rats, ATP receptors were functionally expressed, but the expression disappeared with development. This developmental change occurred earlier in low-threshold than high-threshold cold thermosensors. Most rat cold thermosensors expressed TRPA1 channels, whereas mouse cold thermosensors did not. The broad implications of this study are that it is now feasible to track changes in receptor and ion-channel expression in individual neuronal subclasses as a function of development, learning, disease, or aging. PMID:24469798

Antiviral type I and type III interferon responses in the central nervous system.

Science.gov (United States)

Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

2013-03-15

The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.

Antiviral Type I and Type III Interferon Responses in the Central Nervous System

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Thomas Michiels

2013-03-01

Full Text Available The central nervous system (CNS harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i preventing neuroinvasion and infection of CNS cells; ii the identity of IFN-producing cells in the CNS; iii the antiviral activity of ISGs; and iv the activity of viral proteins of neurotropic viruses that target the IFN pathway.

lin-12 Notch functions in the adult nervous system of C. elegans

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Tucey Tim M

2005-07-01

Full Text Available Abstract Background Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion. Results The spontaneous reversal rate of C. elegans during normal locomotion is constant. Both lin-12 gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by lin-12 activity, because the loss of function defect could be rescued by a wild type lin-12 transgene. Furthermore, overexpression of lin-12 recapitulated the gain-of-function defect. Increasing or decreasing lin-12 activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for lin-12. Although lin-12 is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering lin-12 activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical lin-12 signaling cascade, including the ligand lag-2 and the transcriptional effector lag-1. Finally, the C. elegans AMPA/kainate glutamate receptor homolog glr-1 shows strong genetic interactions with lin-12, suggesting that glr-1 and/or other glutamate gated channels may be targets of lin-12 regulation. Conclusion Our results demonstrate a neuronal role for lin-12 Notch in C. elegans and suggest that lin-12 acutely regulates neuronal physiology to

The Myriad Roles of Miro in the Nervous System: Axonal Transport of Mitochondria and Beyond

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Bingwei eLu

2014-10-01

Full Text Available Mitochondrial rho GTPase (Miro is a mitochondrial outer membrane protein containing two GTPase domains and two helix-loop-helix Ca2+-binding domains called EF hands. Pioneering genetic studies in Drosophila first revealed a key function of Miro in regulating the axonal transport of mitochondria, during which Miro forms a multi-protein transport complex with Milton and Kinesin heavy chain (KHC to link trafficking mitochondria with the microtubule cytoskeleton. Recent studies showed that through binding to the EF hands of Miro and causing conformational changes of Miro and alteration of protein-protein interactions within the transport complex, Ca2+ can alter the engagement of mitochondria with the microtubule (MT/kinesin network, offering one mechanism to match mitochondrial distribution with neuronal activity. Despite the importance of the Miro/Milton/Kinesin complex in regulating mitochondrial transport in metazoans, not all components of the transport complex are conserved in lower organisms, and transport-independent functions of Miro are emerging. Here we review the diverse functions of the evolutionarily conserved Miro proteins that are relevant to the development, maintenance, and functioning of the nervous system and discuss the potential contribution of Miro dysfunction to the pathogenesis of diseases of the nervous system.

Plasticity in the Drosophila larval visual System

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Abud J Farca-Luna

2013-07-01

Full Text Available The remarkable ability of the nervous system to modify its structure and function is mostly experience and activity modulated. The molecular basis of neuronal plasticity has been studied in higher behavioral processes, such as learning and memory formation. However, neuronal plasticity is not restricted to higher brain functions, but may provide a basic feature of adaptation of all neural circuits. The fruit fly Drosophila melanogaster provides a powerful genetic model to gain insight into the molecular basis of nervous system development and function. The nervous system of the larvae is again a magnitude simpler than its adult counter part, allowing the genetic assessment of a number of individual genetically identifiable neurons. We review here recent progress on the genetic basis of neuronal plasticity in developing and functioning neural circuits focusing on the simple visual system of the Drosophila larva.

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.

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Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G; Grison, Alice; Gustincich, Stefano

2016-01-01

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.

IMPACTS OF TISSUE-TYPE PLASMINOGEN ACTIVATOR (TPA ON NEURONAL SURVIVAL

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Arnaud eChevilley

2015-10-01

Full Text Available Tissue-type plasminogen activator (tPA a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central nervous system, tPA displays both neurotrophic and neurotoxic effects. How can the protease mediate such opposite functions remain unclear but several hypotheses have been proposed. These include an influence of the degree of maturity and/or the type of neurons, of the level of tPA, of its origin (endogenous or exogenous or of its form (single chain tPA versus two chain tPA. In this review, we will provide a synthetic snapshot of our current knowledge regarding the natural history of tPA and discuss how it sustains its pleiotropic functions with focus on excitotoxic/ischemic neuronal death and neuronal survival.

Radiation risks to the developing nervous system

International Nuclear Information System (INIS)

Kriegel, H.; Schmahl, W.; Stieve, F.E.; Gerber, G.B.

1986-01-01

A symposium dealing with 'Radiation Risks to the Developing Nervous System' held at Neuherberg, June 18-20, 1985 was organised by the Radiation Protection Programme of the Commission of the European Communities and the Gesellschaft fuer Strahlen- und Umweltforschung mbH. The proceedings of this symposium present up-to-date information on the development of the nervous system and the modifications caused by prenatal radiation there upon. A large part of the proceedings is devoted to the consequences of prenatal irradiation in experimental animals with respect to alterations in morphology, biochemistry and behaviour, to the influence of dose, dose rate and radiation quality and to the question whether damage of the brain can arise from a synergistic action of radiation together with other agents. Since animal models for damage to the human central nervous system have inherent short-comings due to the differences in structure, complexity and development it is discussed how experimental studies could be applied to the human situation. The most recent data on persons exposed in utero at Hiroshima and Nagasaki are reviewed. A round table discussion, published in full, analyses all this information with a view to radiation protection, and defines the areas where future studies are needed. Separate abstracts were prepared for papers in these proceedings. (orig./MG)

Two Classes of Secreted Synaptic Organizers in the Central Nervous System.

Science.gov (United States)

Yuzaki, Michisuke

2018-02-10

Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of pre- and/or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft. These include Lgi1, Cbln1, neuronal pentraxins, Hevin, thrombospondins, and glypicans. Diffusible secreted factors, such as Wnts, fibroblast growth factors, and semaphorins, tend to act from a distance. In contrast, ESPs remain at the synaptic cleft and often help synaptic adhesion and/or accumulation of postsynaptic receptors. Many fundamental questions remain about when, how, and why various synaptic organizers establish and modify the vast numbers of connections during development and throughout life.

Neuronopathic lysosomal storage disorders: Approaches to treat the central nervous system.

Science.gov (United States)

Scarpa, Maurizio; Bellettato, Cinzia Maria; Lampe, Christina; Begley, David J

2015-03-01

Pharmacological research has always focused on developing new therapeutic strategies capable of modifying a disease's natural history and improving patients' quality of life. Despite recent advances within the fields of medicine and biology, some diseases still represent a major challenge for successful therapy. Neuronopathic lysosomal storage disorders, in particular, have high rates of morbidity and mortality and a devastating socio-economic effect. Many of the available therapies, such as enzyme replacement therapy, can reverse the natural history of the disease in peripheral organs but, unfortunately, are still unable to reach the central nervous system effectively because they cannot cross the blood-brain barrier that surrounds and protects the brain. Moreover, many lysosomal storage disorders are characterized by a number of blood-brain barrier dysfunctions, which may further contribute to disease neuropathology and accelerate neuronal cell death. These issues, and their context in the development of new therapeutic strategies, will be discussed in detail in this chapter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Heterogeneity of D-Serine Distribution in the Human Central Nervous System

Science.gov (United States)

Suzuki, Masataka; Imanishi, Nobuaki; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu

2017-01-01

D-serine is an endogenous ligand for N-methyl-D-aspartate glutamate receptors. Accumulating evidence including genetic associations of D-serine metabolism with neurological or psychiatric diseases suggest that D-serine is crucial in human neurophysiology. However, distribution and regulation of D-serine in humans are not well understood. Here, we found that D-serine is heterogeneously distributed in the human central nervous system (CNS). The cerebrum contains the highest level of D-serine among the areas in the CNS. There is heterogeneity in its distribution in the cerebrum and even within the cerebral neocortex. The neocortical heterogeneity is associated with Brodmann or functional areas but is unrelated to basic patterns of cortical layer structure or regional expressional variation of metabolic enzymes for D-serine. Such D-serine distribution may reflect functional diversity of glutamatergic neurons in the human CNS, which may serve as a basis for clinical and pharmacological studies on D-serine modulation. PMID:28604057

Managing Brain Extracellular K(+) during Neuronal Activity

DEFF Research Database (Denmark)

Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

2016-01-01

characteristics required to fulfill their distinct physiological roles in clearance of K(+) from the extracellular space in the face of neuronal activity. Understanding the nature, impact and effects of the various Na(+)/K(+)-ATPase isoform combinations in K(+) management in the central nervous system might...... understanding of the pathological events occurring during disease....

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Buehler, Paul W.; Butt, Omer I. [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); D' Agnillo, Felice, E-mail: felice.dagnillo@fda.hhs.gov [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

2011-06-10

Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

Science.gov (United States)

O'Rourke, Caitriona; Hopper, Colin; MacRobert, Alexander J; Phillips, James B; Woodhams, Josephine H

2017-08-07

Photochemical Internalisation (PCI) is a novel drug delivery technology in which low dose photodynamic therapy (PDT) can selectively rupture endo/lysosomes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release in the treatment of cancer. For PCI to be developed further, it is important to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to PCI treatment in a 3D co-culture system following incubation with photosensitisers: meso-tetraphenylporphine (TPPS 2a ) or tetraphenylchlorin disulfonate (TPCS 2 a) and Bleomycin. Results from the use of 3D co-culture models demonstrate that a cancer cell line PCI30 and satellite glia were more sensitive to PCI than neurons and mixed glial cells, athough neurite length was affected. Neurons in culture survived PCI treatment under conditions sufficient to kill tumour cells, suggesting cancers within or adjacent to nervous system tissue could be treated with this novel technology. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

human immunodeficiency virus and the nervous system

African Journals Online (AJOL)

drclement

pathogenicity, drug resistance and predisposition to ... tropical countries, antiretroviral therapy is not available ... induced peripheral nervous system disorders ... ataxia and intractable vomiting. ... eligibility for chemotherapy and survival after.

Inflammatory and apoptotic remodeling in autonomic nervous system following myocardial infarction.

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Chen Gao

Full Text Available Chronic myocardial infarction (MI triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS, including stellate ganglia (SG and dorsal root ganglia (DRG contribute to increased sympathoexcitation, cardiac dysfunction and arrythmogenesis. ANS modulation is a therapeutic target for arrhythmia associated with cardiac injury. However, the molecular mechanism involved in the pathological remodeling in ANS following cardiac injury remains to be established.In this study, we performed transcriptome analysis by RNA-sequencing in thoracic SG and (T1-T4 DRG obtained from Yorkshire pigs following either acute (3 to 5 hours or chronic (8 weeks myocardial infarction. By differential expression and weighted gene co-expression network analysis (WGCNA, we identified significant transcriptome changes and specific gene modules in the ANS tissues in response to myocardial infarction at either acute or chronic phases. Both differential expressed genes and the member genes of the WGCNA gene module associated with post-infarct condition were significantly enriched for inflammatory signaling and apoptotic cell death. Targeted validation analysis supported a significant induction of inflammatory and apoptotic signal in both SG and DRG following myocardial infarction, along with cellular evidence of apoptosis induction based on TUNEL analysis. Importantly, these molecular changes were observed specifically in the thoracic segments but not in their counterparts obtained from lumbar sections.Myocardial injury leads to time-dependent global changes in gene expression in the innervating ANS. Induction of inflammatory gene expression and loss of neuron cell viability in SG and DRG are potential novel mechanisms contributing to abnormal ANS function which can promote cardiac arrhythmia and pathological remodeling in myocardium.

Sympathetic neurons modulate the beat rate of pluripotent cell-derived cardiomyocytes in vitro.

Science.gov (United States)

Takeuchi, Akimasa; Shimba, Kenta; Mori, Masahide; Takayama, Yuzo; Moriguchi, Hiroyuki; Kotani, Kiyoshi; Lee, Jong-Kook; Noshiro, Makoto; Jimbo, Yasuhiko

2012-12-01

Although stem cell-derived cardiomyocytes have great potential for the therapy of heart failure, it is unclear whether their function after grafting can be controlled by the host sympathetic nervous system, a component of the autonomic nervous system (ANS). Here we demonstrate the formation of functional connections between rat sympathetic superior cervical ganglion (SCG) neurons and pluripotent (P19.CL6) cell-derived cardiomyocytes (P19CMs) in compartmentalized co-culture, achieved using photolithographic microfabrication techniques. Formation of synapses between sympathetic neurons and P19CMs was confirmed by immunostaining with antibodies against β-3 tubulin, synapsin I and cardiac troponin-I. Changes in the beat rate of P19CMs were triggered after electrical stimulation of the co-cultured SCG neurons, and were affected by the pulse frequency of the electrical stimulation. Such changes in the beat rate were prevented when propranolol, a β-adrenoreceptor antagonist, was added to the culture medium. These results suggest that the beat rate of differentiated cardiomyocytes can be modulated by electrical stimulation of connected sympathetic neurons.

Epigenetics, Nervous System Tumors, and Cancer Stem Cells

Energy Technology Data Exchange (ETDEWEB)

Qureshi, Irfan A. [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Mehler, Mark F., E-mail: mark.mehler@einstein.yu.edu [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States)

2011-09-13

Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors.

Epigenetics, Nervous System Tumors, and Cancer Stem Cells

International Nuclear Information System (INIS)

Qureshi, Irfan A.; Mehler, Mark F.

2011-01-01

Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors

Neuronal migration, apoptosis and bipolar disorder.

Science.gov (United States)

Uribe, Ezequiel; Wix, Richard

2012-01-01

Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth and death during this development period. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity?

Science.gov (United States)

Reich, Arno; Spering, Christopher; Schulz, Jörg B

2008-09-01

For over a decade, neuroscientific research has focused on processes of apoptosis and its contribution to the pathophysiology of neurological diseases. In the central nervous system, the degree of intrinsic mitochondrial-mediated apoptotic signaling expresses a cell's individual metabolic stress, whereas activation of the extrinsic death receptor-induced cascade is regarded as a sign of imbalanced cellular networks. Under physiological conditions, most neurons possess death receptors without being sensitive to receptor-mediated apoptosis. This paradox raises two questions: what is the evolutionary advantage of expressing potentially harmful proteins? How is their signaling controlled? This review summarizes the functional relevance of FasL-Fas signaling--a quintessential death ligand/receptor system--in different neurological disease models ranging from traumatic, inflammatory and ischemic to neurodegenerative processes. Furthermore, it outlines alternative non-apoptotic Fas signaling, shedding new light on its neuroplastic capacity. Finally, receptor-proximal regulatory proteins are introduced and identified as potential protagonists of disease-modifying neurological therapies.

Diagnosis abnormalities of limb movement in disorders of the nervous system

Science.gov (United States)

Tymchik, Gregory S.; Skytsiouk, Volodymyr I.; Klotchko, Tatiana R.; Bezsmertna, Halyna; Wójcik, Waldemar; Luganskaya, Saule; Orazbekov, Zhassulan; Iskakova, Aigul

2017-08-01

The paper deals with important issues of diagnosis early signs of diseases of the nervous system, including Parkinson's disease and other specific diseases. Small quantities of violation trajectory of spatial movement of the extremities of human disease at the primary level as the most appropriate features are studied. In modern medical practice is very actual the control the emergence of diseases of the nervous system, including Parkinson's disease. In work a model limbs with six rotational kinematic pairs for diagnosis of early signs of diseases of the nervous system is considered. subject.

Estrogen receptor-alpha and -beta immunoreactive neurons in the brainstem and spinal cord of male and female mice : Relationships to monoaminergic, cholinergic, and spinal projection systems

NARCIS (Netherlands)

VanderHorst, VGJM; Gustafsson, JA; Ulfhake, B

2005-01-01

For many populations of estrogen-sensitive neurons it remains unknown how they are associated with central nervous system circuitries that mediate estrogen-induced modulation of behavioral components. With the use of double-labeling immunohistochemistry and tracing techniques, the relationships of

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

Science.gov (United States)

Gunasekaran, Manojkumar; Chatterjee, Prodyot K.; Shih, Andrew; Imperato, Gavin H.; Addorisio, Meghan; Kumar, Gopal; Lee, Annette; Graf, John F.; Meyer, Dan; Marino, Michael; Puleo, Christopher; Ashe, Jeffrey; Cox, Maureen A.; Mak, Tak W.; Bouton, Chad; Sherry, Barbara; Diamond, Betty; Andersson, Ulf; Coleman, Thomas R.; Metz, Christine N.; Tracey, Kevin J.; Chavan, Sangeeta S.

2018-01-01

The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses. PMID:29755449

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

Directory of Open Access Journals (Sweden)

Manojkumar Gunasekaran

2018-04-01

Full Text Available The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR, dorsal root ganglion (DRG sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM into wild-type (WT mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

Science.gov (United States)

Salton, S R; Fischberg, D J; Dong, K W

1991-05-01

Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.

The larval nervous system of the penis worm Priapulus caudatus (Ecdysozoa).

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Martín-Durán, José M; Wolff, Gabriella H; Strausfeld, Nicholas J; Hejnol, Andreas

2016-01-05

The origin and extreme diversification of the animal nervous system is a central question in biology. While most of the attention has traditionally been paid to those lineages with highly elaborated nervous systems (e.g. arthropods, vertebrates, annelids), only the study of the vast animal diversity can deliver a comprehensive view of the evolutionary history of this organ system. In this regard, the phylogenetic position and apparently conservative molecular, morphological and embryological features of priapulid worms (Priapulida) place this animal lineage as a key to understanding the evolution of the Ecdysozoa (i.e. arthropods and nematodes). In this study, we characterize the nervous system of the hatching larva and first lorica larva of the priapulid worm Priapulus caudatus by immunolabelling against acetylated and tyrosinated tubulin, pCaMKII, serotonin and FMRFamide. Our results show that a circumoral brain and an unpaired ventral nerve with a caudal ganglion characterize the central nervous system of hatching embryos. After the first moult, the larva attains some adult features: a neck ganglion, an introvert plexus, and conspicuous secondary longitudinal neurites. Our study delivers a neuroanatomical framework for future embryological studies in priapulid worms, and helps illuminate the course of nervous system evolution in the Ecdysozoa. © 2015 The Authors.

MicroRNA expression in the adult mouse central nervous system

DEFF Research Database (Denmark)

Bak, Mads; Silahtaroglu, Asli; Møller, Morten

2008-01-01

distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

Melanin-concentrating hormone: unique peptide neuronal systems in the rat brain and pituitary gland

International Nuclear Information System (INIS)

Zamir, N.; Skofitsch, G.; Bannon, M.J.; Jacobowitz, D.M.

1986-01-01

A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimuls (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake

Discriminative staining methods for the nervous system: luxol fast blue--periodic acid-Schiff--hematoxylin triple stain and subsidiary staining methods.

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Goto, N

1987-09-01

This paper describes a new series of staining methods which can discriminatively demonstrate every structure of the nervous system, including axons and capillaries, in animal and human materials. Methods described in this paper consist of one primary stain, luxol fast blue-periodic acid Schiff-hematoxylin (LPH) and six different subsidiary staining methods. The LPH triple stain can precisely differentiate the following structures: neurons (Nissl bodies, cytoplasm, nuclear membrane and nucleolus), various kinds of nuclei (glia, ependyma, endothelium, leucocyte, connective tissue, etc.), myelin sheaths, neuronal processes (axons and dendrites), reacted glial cell bodies (protoplasmic astrocytes, foamy cells, etc.), blood vessels (arteries, veins and capillaries), meninges, intervening connective tissue, erythrocytes, lipofuscin granules, amyloid bodies, and others. Subsidiary staining methods are also described briefly. Applications are discussed in the context of staining technology and neuromorphological research.

Prenatal irradiation: radioinduced apoptosis in developing central nervous system

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Michelin, S.; Perez, M.R.; Barboza, M.

1998-01-01

Severe mental retardation (SMR) is the most significant effect of prenatal irradiation. The high radiosensitivity of developing brain is related with the chronology of morpho genetic phenomena regarding neuroblast proliferation, neuronal differentiation and migration, synaptogenesis and dendritic arborization. Programmed cell death (apoptosis) normally occurs during development in central nervous system (CNS). Apoptosis is a direct result of the expression of specific genes with a final common pathway leading to a characteristic DNA fragmentation pattern. A wide variety of situations and toxic agents have been reported to result in apoptotic death in developing CNS. The aim of this work was the characterization and quantification of apoptosis using an in vitro model of prenatal irradiation. Primary cell cultures from rat brain cortex of 17 days g.a. were irradiated with a gamma source, with doses between 0.2 Gy to 2 Gy. Apoptosis was evaluated 4 hours and 20 hours after irradiation by hematoxylin/eosin, fluorescent microscopy, flow cytometry and DNA electrophoresis. It was also evaluated the neuro protective effect of L-NAME, SOD and glutathion. A dose-dependent increase in apoptotic cell fraction was observed. A protector effect related with the presence of glutathion was observed. (author) [es

Effects of Brazilian scorpion venoms on the central nervous system.

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Nencioni, Ana Leonor Abrahão; Neto, Emidio Beraldo; de Freitas, Lucas Alves; Dorce, Valquiria Abrão Coronado

2018-01-01

In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus , T. bahiensis , T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus , T. silvestres, T. brazilae , T. confluens , T. costatus , T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis . Little information is available regarding the other Brazilian Tityus species.

Multiple myeloma and central nervous system involvement: experience of a Brazilian center

Directory of Open Access Journals (Sweden)

Ana Luiza Miranda Silva Dias

2018-01-01

Full Text Available Introduction: The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. Methods: This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Results: Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Conclusion: Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable. Keywords: Central nervous system, Multiple myeloma, Radiotherapy, Chemotherapy, Prognosis

Nuclear exclusion of transcription factors associated with apoptosis in developing nervous tissue

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R. Linden

1999-07-01

Full Text Available Programmed cell death in the form of apoptosis involves a network of metabolic events and may be triggered by a variety of stimuli in distinct cells. The nervous system contains several neuron and glial cell types, and developmental events are strongly dependent on selective cell interactions. Retinal explants have been used as a model to investigate apoptosis in nervous tissue. This preparation maintains the structural complexity and cell interactions similar to the retina in situ, and contains cells in all stages of development. We review the finding of nuclear exclusion of several transcription factors during apoptosis in retinal cells. The data reviewed in this paper suggest a link between apoptosis and a failure in the nucleo-cytoplasmic partition of transcription factors. It is argued that the nuclear exclusion of transcription factors may be an integral component of apoptosis both in the nervous system and in other types of cells and tissues.

Neuronal network analyses: premises, promises and uncertainties

OpenAIRE

Parker, David

2010-01-01

Neuronal networks assemble the cellular components needed for sensory, motor and cognitive functions. Any rational intervention in the nervous system will thus require an understanding of network function. Obtaining this understanding is widely considered to be one of the major tasks facing neuroscience today. Network analyses have been performed for some years in relatively simple systems. In addition to the direct insights these systems have provided, they also illustrate some of the diffic...

CT findings of central nervous system in congenital syphilis infant

International Nuclear Information System (INIS)

Yang Cheng; Yang Xinghui; Wang Man

2005-01-01

Objective: To investigate the CT features of the central nervous system in congenital syphilis infant. Methods: CT findings of central nervous system in 11 infants with clinically proved congenital syphilis were analyzed retrospectively. Results: CT findings in 10 syphilis neonates were diffuse hypodense lesions in the white matter, with subarachnoid and intra-encephalic hemorrhage in 3 and 1 cases, respectively. One 2-month-old syphilis infant case and 5 cases of follow-up after 45 days to 6 months of treatment demonstrated bilateral widened sulci and cistern with enlarged ventricles in 3 of them. Conclusion: CT findings of the central nervous system in congenital syphilis infant are similar to those of hypoxic-ischemic encephalopathy in neonates, and extra-encephalic hydrocephalus or brain hypogenesis ensues later on. (authors)

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa.

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Bertapelle, Carla; Polese, Gianluca; Di Cosmo, Anna

2017-06-01

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, reviled cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis. © 2017 Wiley Periodicals, Inc.

Expression of canine distemper virus receptor nectin-4 in the central nervous system of dogs.

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Pratakpiriya, Watanyoo; Ping Teh, Angeline Ping; Radtanakatikanon, Araya; Pirarat, Nopadon; Thi Lan, Nguyen; Takeda, Makoto; Techangamsuwan, Somporn; Yamaguchi, Ryoji

2017-03-23

Canine distemper virus (CDV) exhibits lymphotropic, epitheliotropic, and neurotropic nature, and causes a severe systemic infection in susceptible animals. Initially, signaling lymphocyte activation molecule (SLAM) expressed on immune cells has been identified as a crucial cellular receptor for CDV. Currently, nectin-4 expressed in epithelia has been shown to be another receptor for CDV. Our previous study demonstrated that neurons express nectin-4 and are infected with CDV. In this study, we investigated the distribution pattern of nectin-4 in various cell types in the canine central nervous system and showed its relation to CDV infection to further clarify the pathology of disease. Histopathological, immunohistochemical and immunofluorescent analyses were done using formalin-fixed paraffin-embedded tissues of CDV-infected dogs. Dual staining of nectin-4 and CDV antigen or nectin-4 and brain cell markers was performed. Nectin-4 was detected in ependymal cells, epithelia of choroid plexus, meningeal cells, neurons, granular cells, and Purkinje's cells. CDV antigens were detected in these nectin-4-positive cells, further suggesting contribution of nectin-4 for the CDV neurovirulence. On the other hand, astrocytes did not express nectin-4, although they were frequently infected with CDV. Since astrocytes are negative for SLAM expression, they must express an unidentified CDV receptor, which also contributes to CDV neurovirulence.

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

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Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

Directory of Open Access Journals (Sweden)

Petra Maria Hermann

2014-12-01

Full Text Available TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (peroxidation of membrane lipids and activation of phospholipase A2 (PLA2 enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the Biology of cognitive aging we (1 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and (2 recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System.

Science.gov (United States)

Takenaka, Akiko; Sato, Hiroki; Ikeda, Fusako; Yoneda, Misako; Kai, Chieko

2016-10-15

In the current study, we generated recombinant chimeric canine distemper viruses (CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an avirulent strain expressing enhanced green fluorescent protein (EGFP) with those of a mouse-adapted neurovirulent strain. An in vitro experimental infection indicated that the chimeric CDVs possessing the H gene derived from the mouse-adapted CDV acquired infectivity for neural cells. These cells lack the CDV receptors that have been identified to date (SLAM and nectin-4), indicating that the H protein defines infectivity in various cell lines. The recombinant viruses were administered intracerebrally to 1-week-old mice. Fatal neurological signs of disease were observed only with a recombinant CDV that possessed both the H and P genes of the mouse-adapted strain, similar to the parental mouse-adapted strain, suggesting that both genes are important to drive virulence of CDV in mice. Using this recombinant CDV, we traced the intracerebral propagation of CDV by detecting EGFP. Widespread infection was observed in the cerebral hemispheres and brainstems of the infected mice. In addition, EGFP fluorescence in the brain slices demonstrated a sequential infectious progression in the central nervous system: CDV primarily infected the neuroependymal cells lining the ventricular wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and it then progressed to an extensive infection of the brain surface, followed by the parenchyma and cortex. In the hippocampal formation, CDV spread in a unidirectional retrograde pattern along neuronal processes in the hippocampal formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse model demonstrated that the main target cells of CDV are neurons in the acute phase and that the virus spreads via neuronal transmission pathways in the hippocampal formation. CDV is the etiological agent of distemper in dogs and other carnivores, and in

Thiophene Scaffold as Prospective Central Nervous System Agent: A Review.

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Deep, Aakash; Narasimhan, Balasubramanian; Aggarwal, Swati; Kaushik, Dhirender; Sharma, Arun K

2016-01-01

Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important. Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Among various classes of heterocyclic compounds that have potential central nervous system activity, thiophene is the most important one. In the largely escalating chemical world of heterocyclic compounds showing potential pharmacological character, thiophene nucleus has been recognized as the budding entity. Seventeen Papers were included in this review article to define the central nervous system potential of thiophene. This review article enlightens the rationalized use and scope of thiophene scaffold as novel central nervous system activity such as anticonvulsant, acetylcholinesterase inhibitor, cyclin-dependent kinase 5 (cdk5/p25) inhibitors, CNS depressant, capability to block norepinephrine, serotonin and dopamine reuptake by their respective transporters etc. The Finding of this review confirm the importance of thiophene scaffold as potential central nervous system agents. From this outcome, ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential may be derived.

Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.

Science.gov (United States)

Wehrwein, Erica A; Orer, Hakan S; Barman, Susan M

2016-06-13

Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Central nervous system complications in non-Hodgkin-lymphomas and radiotherapy

International Nuclear Information System (INIS)

Liffers, R.

1981-01-01

261 case historys of malignant non-Hodgkin-lymphomas were analysed in the years from 1969 until 1978 in the 'Radiologische Universitaetsklinik Kiel'/West-Germany. 18 Patients got a central nervous complication of Non Hodgkin-Lymphoma earlier or later, a percentage of about 7. There were 7 cases of lymphoblastic lymphoma (LB), a percentage of 10 for this entity. In the group of immunoblastic lymphoma (IB) 6 cases of central nervous infiltration were detected, that is a ratio of 7.7 percent. 4 case histories M. Brill-Symmers (CC/CB) were complicated by central nervous dissemination, a percentage of 5.3. Patients with lymphoblastic lymphoma have the highest risk of central nervous complication. The beginning of central nervous dissemination in the single case histories is very different between the histological groups. Patients with lymphoblastic lymphoma suffered from central nervous complication in an early phase of history, in cases of M. Brill-Symmers central nervous infiltration can occur also in a late phase. The results may determine the discussion about stratifying of radiotherapy. Early radiotherapy including central nervous system may be discussed and investigated in special histological entities of malignant non-Hodgkin-lymphoma. (orig.) [de

Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.

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Machado, Carolina Barcellos; Kanning, Kevin C; Kreis, Patricia; Stevenson, Danielle; Crossley, Martin; Nowak, Magdalena; Iacovino, Michelina; Kyba, Michael; Chambers, David; Blanc, Eric; Lieberam, Ivo

2014-02-01

Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.

Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

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Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-12-06

...] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...) and/or abnormal vascularity (abnormal blood supply and circulation) of the central nervous system. The...

Nervous control of photophores in luminescent fishes.

Science.gov (United States)

Zaccone, Giacomo; Abelli, Luigi; Salpietro, Lorenza; Zaccone, Daniele; Macrì, Battesimo; Marino, Fabio

2011-07-01

Functional studies of the autonomic innervation in the photophores of luminescent fishes are scarce. The majority of studies have involved either the stimulation of isolated photophores or the modulatory effects of adrenaline-induced light emission. The fish skin is a highly complex organ that performs a wide variety of physiological processes and receives extensive nervous innervations. The latter includes autonomic nerve fibers of spinal sympathetic origin having a secretomotor function. More recent evidence indicates that neuropeptide-containing nerve fibers, such as those that express tachykinin and its NK1 receptor, neuropeptide Y, or nitric oxide, may also play an important role in the nervous control of photophores. There is no anatomical evidence that shows that nNOS positive (nitrergic) neurons form a population distinct from the secretomotor neurons with perikarya in the sympathetic ganglia. The distribution and function of the nitrergic nerves in the luminous cells, however, is less clear. It is likely that the chemical properties of the sympathetic postganglionic neurons in the ganglia of luminescent fishes are target-specific, such as observed in mammals. Copyright © 2010 Elsevier GmbH. All rights reserved.

Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

Science.gov (United States)

Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-09-01

Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

Reorganization of the human central nervous system.