Showing papers on "Nervous system published in 2006"
TL;DR: It is shown that a brain-specific microRNA, miR-134>, is localized to the synapto-dendritic compartment of rat hippocampal neurons and negatively regulates the size of dendritic spines—postsynaptic sites of excitatory synaptic transmission.
Abstract: MicroRNAs are small, non-coding RNAs that control the translation of target messenger RNAs, thereby regulating critical aspects of plant and animal development. In the mammalian nervous system, the spatiotemporal control of mRNA translation has an important role in synaptic development and plasticity. Although a number of microRNAs have been isolated from the mammalian brain, neither the specific microRNAs that regulate synapse function nor their target mRNAs have been identified. Here we show that a brain-specific microRNA, miR-134, is localized to the synapto-dendritic compartment of rat hippocampal neurons and negatively regulates the size of dendritic spines--postsynaptic sites of excitatory synaptic transmission. This effect is mediated by miR-134 inhibition of the translation of an mRNA encoding a protein kinase, Limk1, that controls spine development. Exposure of neurons to extracellular stimuli such as brain-derived neurotrophic factor relieves miR-134 inhibition of Limk1 translation and in this way may contribute to synaptic development, maturation and/or plasticity.
1,746 citations
TL;DR: Diffusion tensor imaging (DTI) is a recently developed MRI technique that can measure macroscopic axonal organization in nervous system tissues and several applications are introduced, including visualization of axonal tracts in myelin and axonal injuries as well as human brain and mouse embryonic development.
1,593 citations
TL;DR: Investigation of the gastric myenteric and submucosal plexuses in 150 microm cryosections and 8 microm paraffin sections from five autopsy individuals found alpha-synuclein immunoreactive inclusions were found in neurons of the subMucosal Meissner plexus, whose axons could provide the first link in an uninterrupted series of susceptible neurons that extend from the enteric to the central nervous system.
1,147 citations
TL;DR: Activity has similar roles in the incorporation of newly born neurons in the adult nervous system, suggesting that there are general rules underlying activity-dependent development.
Abstract: The construction of the brain during embryonic development was thought to be largely independent of its electrical activity. In this view, proliferation, migration and differentiation of neurons are driven entirely by genetic programs and activity is important only at later stages in refinement of connections. However, recent findings demonstrate that activity plays essential roles in early development of the nervous system. Activity has similar roles in the incorporation of newly born neurons in the adult nervous system, suggesting that there are general rules underlying activity-dependent development. The extensive involvement of activity makes it likely that it is required at all developmental stages as a necessary partner with genetic programs.
692 citations
TL;DR: It is shown that in two mouse models of motoneuron disease, axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear, and that mot oneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.
Abstract: Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally defined selective vulnerabilities of distinct synapses or axons. Here we derive a quantitative topographic map of muscle innervation in the hindlimb. We show that in two mouse models of motoneuron disease (G93A SOD1 and G85R SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Axonal vulnerability leads to synaptic vesicle stalling and accumulation of BC12a1-a, an anti-apoptotic protein. It is alleviated by ciliary neurotrophic factor and triggers proteasome-dependent pruning of peripheral axon branches. Thus, motoneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.
611 citations
TL;DR: It is shown that Bace1 regulates the process of myelination and myelin sheath thickness in the central and peripheral nerves and that processed neuregulin-1 regulates myelinations by means of phosphorylation of Akt in myelin-forming cells.
Abstract: Bace1 is an endopeptidase that cleaves the amyloid precursor protein at the beta-secretase site. Apart from this cleavage, the functional importance of Bace1 in other physiological events is unknown. We show here that Bace1 regulates the process of myelination and myelin sheath thickness in the central and peripheral nerves. In Bace1-null mice, the process of myelination was delayed and myelin thickness was markedly reduced, indicating that genetic deletion of Bace1 causes hypomyelination. Bace1-null mice also showed altered neurological behaviors such as elevated pain sensitivity and reduced grip strength. Further mechanistic studies showed an altered neuregulin-Akt signaling pathway in Bace1-null mice. Full-length neuregulin-1 was increased and its cleavage product was decreased in the CNS of Bace1-null mice. Furthermore, phosphorylated Akt was also reduced. Based upon these and previous studies, we postulate that neuronally enriched Bace1 cleaves neuregulin-1 and that processed neuregulin-1 regulates myelination by means of phosphorylation of Akt in myelin-forming cells.
590 citations
TL;DR: The development of the human brain is characterized by a protracted, neatly orchestrated chain of specific ontogenetic events, which have consequences for vulnerability to adverse conditions, for diagnostics and for physiotherapeutical intervention.
515 citations
TL;DR: It is shown that transected Drosophila axons undergo injury-induced degeneration that is morphologically similar to Wallerian degeneration in mammals and can be suppressed by the neuroprotective mouse Wlds protein.
447 citations
TL;DR: It is proposed that voluntary slow deep breathing functionally resets the autonomic nervous system through stretch-induced inhibitory signals and hyperpolarization currents propagated through both neural and non-neural tissue which synchronizes neural elements in the heart, lungs, limbic system and cortex.
401 citations
TL;DR: Observations on somatosensory evoked potentials in 35 healthy subjects, recorded by Dawson’s methods, as well as results in 56 patients of the National Hospital, Queen Square, London, in whom evoked possibles were investigated during 1958 to 1960 are reported.
Abstract: Methods commonly used in animals to record, directly from the surface of the cortex, the potentials which are evoked by sensory stimuli are not satisfactory for investigating evoked responses in man. Dawson ( 1947, 1954) was the first to devise methods which made it possible to see evoked potentials in records from electrodes on the scalp and to adequately describe the human cerebral evoked response. The following paper reports observations on somatosensory evoked potentials in 35 healthy subjects, recorded by Dawson’s methods, as well as results in 56 patients of the National Hospital, Queen Square, London, in whom evoked potentials were investigated during 1958 to 1960. In patients who showed impaired sensation due to lesions affecting peripheral nerves, spinal cord, or brain, the results have been correlated with the modality and the severity of the sensory loss and with the sites of lesions.
396 citations
TL;DR: Many neurotransmitters including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide and neuropeptides are involved in the neural control of the LUT.
Abstract: Storage and periodic expulsion of urine is regulated by a neural control system in the brain and spinal cord that coordinates the reciprocal activity of two functional units in the lower urinary tract (LUT): (a) a reservoir (the urinary bladder) and (b) an outlet (bladder neck, urethra and striated muscles of the urethral sphincter). Control of the bladder and urethral outlet is dependent on three sets of peripheral nerves: parasympathetic, sympathetic and somatic nerves that contain afferent as well as efferent pathways. Afferent neurons innervating the bladder have A-δ or C-fibre axons. Urine storage reflexes are organized in the spinal cord, whereas voiding reflexes are mediated by a spinobulbospinal pathway passing through a coordination centre (the pontine micturition centre) located in the brainstem. Storage and voiding reflexes are activated by mechanosensitive A-δ afferents that respond to bladder distension. Many neurotransmitters including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide and neuropeptides are involved in the neural control of the LUT. Injuries or diseases of the nervous system as well as disorders of the peripheral organs can produce LUT dysfunctions including: (1) urinary frequency, urgency and incontinence or (2) inefficient voiding and urinary retention. Neurogenic detrusor overactivity is triggered by C-fibre bladder afferent axons, many of which terminate in the close proximity to the urothelium. The urothelial cells exhibit ‘neuron-like' properties that allow them to respond to mechanical and chemical stimuli and to release transmitters that can modulate the activity of afferent nerves.
TL;DR: Since they may play a prominent role in certain neurologic disorders, such as ischemia-reperfusion injury, Alzheimer's disease, spinal cord injury and sensory neuropathies, the pathological role and potential therapeutic exploitation of P2X(7) receptors are discussed.
TL;DR: Gene expression in neurons persists for a long time, even at postnatal stages, after electroporation, which could be used to analyze roles of genes not only in embryonic development but also in higher order function of the nervous system, such as learning.
Abstract: This protocol describes a basic method for in vivo electroporation in the nervous system of embryonic mice. Delivery of electric pulses following microinjection of DNA into the brain ventricle or the spinal cord central canal enables efficient transfection of genes into the nervous system. Transfection is facilitated by forceps-type electrodes, which hold the uterus and/or the yolk sac containing the embryo. More than ten embryos in a single pregnant mouse can be operated on within 30 min. More than 90% of operated embryos survive and more than 90% of these survivors express the transfected genes appropriately. Gene expression in neurons persists for a long time, even at postnatal stages, after electroporation. Thus, this method could be used to analyze roles of genes not only in embryonic development but also in higher order function of the nervous system, such as learning.
01 Jan 2006
TL;DR: In this paper, the structural and pharmacological features of the P2X7 receptor, as well as its cell-type specific localization in the nervous system are reviewed. And the participation of P2x7 receptors in distinct neuronal, astroglial and microglial functions are described.
Abstract: P2X7 receptors are ligand-gated ion channels, expressed as homo-oligomeric assemblies of individual subunits. They are widely distributed at immunocompetent cells of the central and peripheral nervous system and are believed to be primarily involved in host-defense reaction. However, a growing amount of evidence indicates that their signaling role in the brain is more widespread than previously anticipated. In this paper, we review the present knowledge on the structural and pharmacological features of the P2X7 receptor, as well as its cell-type specific localization in the nervous system. Subsequently, the participation of P2X7 receptors in distinct neuronal, astroglial and microglial functions are described. Finally, since they may play a prominent role in certain neurologic disorders, such as ischemia-reperfusion injury, Alzheimer’s disease, spinal cord injury and sensory neuropathies, the pathological role and potential therapeutic exploitation of P2X7 receptors are also discussed. # 2006 Elsevier Ltd. All rights reserved.
TL;DR: Evidence that an anatomically separate population of nonhypophysiostropic TRH neurons in the anterior parvocellular subdivision of the PVN is integrated into the leptin regulatory control system by the same arcuate nucleus neuronal populations that innervate hypophysiotropicTRH neurons, raises the possibility that anterior parVOcellular TRH neuron may be involved.
Abstract: Thyrotropin-releasing hormone (TRH) has an important role in the regulation of energy homeostasis not only through effects on thyroid function orchestrated through hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN), but also through central effects on feeding behavior, thermogenesis, locomotor activation and autonomic regulation Hypophysiotropic TRH neurons are located in the medial and periventricular parvocellular subdivisions of the PVN and receive direct monosynaptic projections from two, separate, populations of leptin-responsive neurons in the hypothalamic arcuate nucleus containing either alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), peptides that promote weight loss and increase energy expenditure, or neuropeptide Y (NPY) and agouti-related protein (AGRP), peptides that promote weight gain and reduce energy expenditure During fasting, the reduction in TRH mRNA in hypophysiotropic neurons mediated by suppression of alpha-MSH/CART simultaneously with an increase in NPY/AGRP gene expression in arcuate nucleus neurons contributes to the fall in circulating thyroid hormone levels, presumably by increasing the sensitivity of the TRH gene to negative feedback inhibition by thyroid hormone Endotoxin administration, however, has the paradoxical effect of increasing circulating levels of leptin and melanocortin signaling and CART gene expression in arcuate nucleus neurons, but inhibiting TRH gene expression in hypophysiotropic neurons This may be explained by an overriding inhibitory effect of endotoxin to increase type 2 iodothyroine deiodinase (D2) in a population of specialized glial cells, tanycytes, located in the base and infralateral walls of the third ventricle By increasing the conversion of T4 into T3, tanycytes may increase local tissue concenetrations of thyroid hormone, and thereby induce a state of local tissue hyperthyroidism in the region of hypophysisotrophic TRH neurons Other regions of the brain may also serve as metabolic sensors for hypophysiostropic TRH neurons including the ventrolateral medulla and dorsomedial nucleus of the hypothalamus that have direct monosynaptic projections to the PVN TRH also exerts a number of effects within the central nervous system that may contribute to the regulation of energy homeostasis Included are an increase in core body temperature mediated through neurons in the anterior hypothalamic-preoptic area that coordinate a variety of autonomic responses; arousal and locomotor activation through cholinergic and dopaminergic mechanisms on the septum and nucleus accumbens, respectively; and regulation of the cephalic phase of digestion While the latter responses are largely mediated through cholinergic mechanisms via TRH neurons in the brainstem medullary raphe and dorsal motor nucleus of the vagus, effects of TRH on autonomic loci in the hypothalamic PVN may also be important Contrary to the actions of T3 to increase appetite, TRH has central effects to reduce food intake in normal, fasting and stressed animals The precise locus where TRH mediates this response is unknown However, evidence that an anatomically separate population of nonhypophysiotropic TRH neurons in the anterior parvocellular subdivision of the PVN is integrated into the leptin regulatory control system by the same arcuate nucleus neuronal populations that innervate hypophysiotropic TRH neurons, raises the possibility that anterior parvocellular TRH neurons may be involved, possibly through interactions with the limbic nervous system
TL;DR: In this paper, the authors showed that skin-derived precursors (SKPs) represent a source of functional, myelinating Schwann cells, and demonstrated that SKPs can generate functional neural progeny in response to appropriate neural crest cues.
Abstract: Although neural stem cells hold considerable promise for treatment of the injured or degenerating nervous system, their current human sources are embryonic stem cells and fetally derived neural tissue. Here, we asked whether rodent and human skin-derived precursors (SKPs), neural crest-related precursors found in neonatal dermis, represent a source of functional, myelinating Schwann cells. Specifically, cultured SKPs responded to neural crest cues such as neuregulins to generate Schwann cells, and these Schwann cells proliferated and induced myelin proteins when in contact with sensory neuron axons in culture. Similar results were obtained in vivo; 6 weeks after transplantation of naive SKPs or SKP-derived Schwann cells into the injured peripheral nerve of wild-type or shiverer mutant mice (which are genetically deficient in myelin basic protein), the majority of SKP-derived cells had associated with and myelinated axons. Naive rodent or human SKPs also generated Schwann cells that myelinated CNS axons when transplanted into the dysmyelinated brain of neonatal shiverer mice. Thus, neonatal SKPs generate functional neural progeny in response to appropriate neural crest cues and, in so doing, provide a highly accessible source of myelinating cells for treatment of nervous system injury, congenital leukodystrophies, and dysmyelinating disorders.
TL;DR: It is indicated that the autonomic nuclei of the spinal cord and the PANS belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves.
Abstract: Studies on cases with incidental Lewy body disease (ILBD) suggest that alpha-synuclein (alphaSN) pathology of Parkinson's disease (PD) starts in lower brainstem nuclei and in the olfactory bulb. However, medullary structures as the induction site of alphaSN pathology have been questioned as large parts of the nervous system, including the spinal cord and the peripheral autonomic nervous system (PANS), have not been examined in ILBD. Thus, the time course of PD lesions in the spinal cord or PANS in relation to medullary lesions remains unknown. We collected 98 post mortem cases with no reference to PD-associated symptoms on clinical records. alphaSN pathology was found in the central nervous system, including the spinal cord, and in the PANS in 17 (17.3%) cases. alphaSN pathology was encountered in autonomic nuclei of the thoracic spinal cord, brainstem and olfactory nerves in 17/17, in sacral parasympathetic nuclei in 15/16, in the myenteric plexus of oesophagus in 14/17, in sympathetic ganglia in 14/17, and in the vagus nerve in 12/16 cases. In addition to the thoracic lateral horns, a high number of alphaSN lesions was also found in non-autonomic spinal cord nuclei. Considering supraspinal structures our cases corresponded roughly to the recently described sequential order of alphaSN involvement in PD. Our study indicates, however, that the autonomic nuclei of the spinal cord and the PANS belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves. A larger cohort of ILBD cases will be needed to pinpoint the precise induction site of alphaSN pathology among these structures.
TL;DR: It is suggested that CB2 agonists may elicit their analgesic effect by acting not only at non‐neuronal peripheral sites but also at neural level, making CB2 an attractive target for chronic pain treatment.
Abstract: In mouse the cannabinoid receptor 2 (CB2) agonists L768242 and (+)-AM1241, at doses of 30 mg/kg i.p. and 1 and 3 mg/kg i.v., respectively, reduced the second phase of nocifensive behaviors elicited by formalin intraplantar injection. This effect was counteracted by the selective CB2 antagonist SR144528 (1 mg/kg i.p.). In rat (+)-AM1241 (3 and 6 mg/kg i.v.) and L768242 (30 mg/kg i.p.) reduced allodynia elicited by L5-L6 spinal nerve ligation. SR144528 reverted these effects, supporting a CB2-mediated action. To clarify the mechanisms underlying these effects we investigated CB2 gene expression and function in the nervous system. CB2 mRNA was expressed in spinal cord and dorsal root ganglia (DRG) of both sham and neuropathic rats and was up-regulated in the ipsilateral spinal cord of neuropathic rats. Expression studies demonstrated the presence of CB2 mRNA in culture of spinal cord microglia. A biomarker, CGRP, was used to investigate modulation of DRG primary afferents by CB2 agonists. Both L768242 and (+)-AM1241 dose dependently (EC50 of 3.6 and 4.5 nM, respectively) reduced capsaicin-induced calcitonin gene-related peptide (CGRP) release. Coadministration of SR144528 resulted in a rightforward shift (pKB 8.1 and 8.2 for (+)-AM1241 and L768242, respectively) of the dose-response curve. Experiments on capsaicin-induced CGRP release in tissue from CB1-/- mice ruled out a CB1-mediated effect. These results confirm that CB2 is present in the central nervous system and suggest that CB2 agonists may elicit their analgesic effect by acting not only at non-neuronal peripheral sites but also at neural level, making CB2 an attractive target for chronic pain treatment.
TL;DR: It is shown that proneural genes have an intricate pattern of expression in the ventricular zone of the ventral midbrain, where mesencephalic dopaminergic neurons are generated, and that Ngn2 is uniquely required for the development of midbrain dopamine neurons.
Abstract: Proneural genes are crucial regulators of neurogenesis and subtype specification in many areas of the nervous system; however, their function in dopaminergic neuron development is unknown. We report that proneural genes have an intricate pattern of expression in the ventricular zone of the ventral midbrain, where mesencephalic dopaminergic neurons are generated. Neurogenin 2 (Ngn2) and Mash1 are expressed in the ventral midline, while Ngn1, Ngn2 and Mash1 are co-localized more laterally in the ventricular zone. Ngn2 is also expressed in an intermediate zone immediately adjacent to the ventricular zone at the ventral midline. To examine the function of these genes, we analyzed mutant mice in which one or two of these genes were deleted (Ngn1, Ngn2 and Mash1) or substituted (Mash1 in the Ngn2 locus). Our results demonstrate that Ngn2 is required for the differentiation of Sox2(+) ventricular zone progenitors into Nurr1(+) postmitotic dopaminergic neuron precursors in the intermediate zone, and that it is also likely to be required for their subsequent differentiation into tyrosine hydroxylase-positive dopaminergic neurons in the marginal zone. Although Mash1 normally has no detectable function in dopaminergic neuron development, it could partially rescue the generation of dopaminergic neuron precursors in the absence of Ngn2. These results demonstrate that Ngn2 is uniquely required for the development of midbrain dopaminergic neurons.
TL;DR: Invertebrate model organisms such as Drosophila have excellent potential to add to the understanding of fundamental aspects of glial biology, and several developmental, morphological and functional similarities are highlighted.
TL;DR: An open-access gene expression database analyzed for more than 2,000 genes on mouse nervous system tissue in the coronal, sagittal, and transverse orientation representing multiple developmental ages is described.
Abstract: This article describes an open-access gene expression database analyzed for more than 2,000 genes on mouse nervous system tissue in the coronal, sagittal, and transverse orientation representing multiple developmental ages.
TL;DR: NSC grafts can survive well in a neurodegenerative environment and exert powerful clinical effects; at least a portion of these effects may be related to the ability of these grafts to express and release motor neuron growth factors delivered to host motor neurons via graft-host connections.
Abstract: Background Experimental therapeutics for degenerative and traumatic diseases of the nervous system have been recently enriched with the addition of neural stem cells (NSCs) as alternatives to fetal tissues for cell replacement. Neurodegenerative diseases present the additional problem that cell death signals may interfere with the viability of grafted cells. The adult spinal cord raises further challenges for NSC differentiation because of lack of intrinsic developmental potential and the negative outcomes of several prior attempts. Method NSCs from human fetal spinal cord were grafted into the lumbar cord of SOD1 G93A rats. The differentiation fate of grafted NSCs and their effects on motor neuron number, locomotor performance, disease onset, and survival trends/longevity were assessed. Trophic mechanisms of observed clinical effects were explored with molecular and cellular methodologies. Result Human NSCs showed extensive differentiation into neurons that formed synaptic contacts with host nerve cells and expressed and released glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. NSC grafts delayed the onset and progression of the fulminant motor neuron disease typical of the rat SOD1 G93A model and extended the lifespan of these animals by more than 10 days, despite the restricted grafting schedule that was limited to the lumbar protuberance. Conclusion NSC grafts can survive well in a neurodegenerative environment and exert powerful clinical effects; at least a portion of these effects may be related to the ability of these grafts to express and release motor neuron growth factors delivered to host motor neurons via graft-host connections.
TL;DR: Neuroinflammation is a proinflammatory cytokine-mediated process that can be provoked by systemic tissue injury but it is most often associated with direct injury to the nervous system.
TL;DR: Compared to controls, animals receiving SCI exhibited injury severity-specific deficits in forelimb, locomotor, and hindlimb function persisting for 6-weeks post-SCI, which is a behavioral and histological model for both gray and white matter damage caused by contusive SCI.
Abstract: Most experimental studies of spinal cord injury (SCI) in rats damage the thoracic cord, with the consequent functional loss being due to interruption of long tracts connecting the caudal spinal cord to the rostral nervous system. Less work has been done evaluating injury to the cervical cord, even though it is the most common level of human SCI. In addition to the long tracts, the cervical spinal cord contains the sensory and motor neurons responsible for upper extremity function. The purpose of this study was to further develop a rat model of cervical spinal cord contusion injury using a modified NYU/MASCIS weight drop device. Mild (6.25 mm) and moderate (12.5 mm) C5 unilateral injuries were produced. Behavioral recovery was examined using a grooming test, a paw preference test, a walkway test (The Catwalk), and a horizontal ladder test. Histological outcome measures included sparing at the lesion epicenter, sparing throughout the extent of the lesion, quantification of myelin loss rostral and caudal to the lesion, and motor neuron counts. Compared to controls, animals receiving SCI exhibited injury severity-specific deficits in forelimb, locomotor, and hindlimb function persisting for 6-weeks post-SCI. Histological analysis revealed ipsilateral containment of the injury, and differentiation between groups on all measures except motor neuron counts. This model has many advantages: (1) minimal animal care requirements post-SCI, (2) within subject controls, (3) functional loss involves primarily the ipsilateral forelimb, and (4) it is a behavioral and histological model for both gray and white matter damage caused by contusive SCI.
TL;DR: The recent discovery that BDNF upregulation in the DRG and spinal cord contributes to chronic pain hypersensitivity indicates that blocking BDNF in sensory neurons could provide a fruitful strategy for the development of novel analgesics.
TL;DR: All symptoms that constitute the nosologic entity of rhinitis can be triggered through neural pathways, and upregulation of the nasal nervous system can occur at various levels of the reflex pathways, resulting in exaggerated responses (neural hyperresponsiveness), as well as in increased capacity for generation of neurogenic inflammation.
Abstract: The nose provides defensive and homeostatic functions requiring rapid responses to physical and chemical stimuli. As a result, it is armed with a complex nervous system that includes sensory, parasympathetic, and sympathetic nerves. Sensory nerves transmit signals from the mucosa, generating sensations, such as pruritus; motor reflexes, such as sneezing; and parasympathetic and sympathetic reflexes that affect the glandular and vascular nasal apparatuses. Reflexes directed to the nose are also generated by inputs from other body regions. Hence all symptoms that constitute the nosologic entity of rhinitis can be triggered through neural pathways. In addition, neural signals generated in the nose can influence distal physiology, such as that of the bronchial tree and the cardiovascular system. Neural function can be chronically upregulated in the presence of mucosal inflammation, acutely with an allergic reaction, or even in the absence of inflammation, as in cases of nonallergic rhinitis. Upregulation of the nasal nervous system can occur at various levels of the reflex pathways, resulting in exaggerated responses (neural hyperresponsiveness), as well as in increased capacity for generation of neurogenic inflammation, a phenomenon that depends on the release of neuropeptides on antidromic stimulation of nociceptive sensory nerves. The molecular mechanisms of hyperresponsiveness are not understood, but several inflammatory products appear to be playing a role. Neurotrophins, such as the nerve growth factor, are prime candidates as mediators of neural hyperresponsiveness. The many interactions between the nervous and immune systems contribute to nasal physiology but also to nasal disease.
TL;DR: Recent findings deciphering the diverse functions of NF-kappaB in NS development and activity are described, which range from the control of cell growth, survival and inflammatory response to synaptic plasticity, behavior and cognition.
TL;DR: In this article, the role of glia in the synthesis and metabolism of steroids and the functional implications of glial steroidogenesis are examined, including role of nuclear receptors and the mechanisms of membrane and cytoplasmic signaling mediated by changes in intracellular calcium levels and activation of signaling kinases.
Abstract: Hormonal and locally produced steroids act in the nervous system as neuroendocrine regulators, as trophic factors and as neuromodulators and have a major impact on neural development and function. Glial cells play a prominent role in the local production of steroids and in the mediation of steroid effects on neurons and other glial cells. In this review, we examine the role of glia in the synthesis and metabolism of steroids and the functional implications of glial steroidogenesis. We analyze the mechanisms of steroid signaling on glia, including the role of nuclear receptors and the mechanisms of membrane and cytoplasmic signaling mediated by changes in intracellular calcium levels and activation of signaling kinases. Effects of steroids on functional parameters of glia, such as proliferation, myelin formation, metabolism, cytoskeletal reorganization, and gliosis are also reviewed, as well as the implications of steroid actions on glia for the regulation of synaptic function and connectivity, the regulation of neuroendocrine events, and the response of neural tissue to injury.
TL;DR: The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities and attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of theSNS on inflammatory disease of the gut.
Abstract: The nervous system in the intestine controls motility, secretion, sensory perception, and immune function. Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut. This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation. The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities. Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT). The SNS has pro- and anti-inflammatory functions. Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course. This review attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of the SNS on inflammatory disease of the gut.
TL;DR: The detection of a gradient of netrin-1 protein supports the operation of long-range chemotropic mechanisms in the developing nervous system.
Abstract: Gradients of diffusible long-range attractant and repellent proteins have been proposed to guide growing axons during nervous system development, but such gradients have never been visualized directly. In the embryonic spinal cord, commissural axons pioneer a circumferential trajectory to the floor plate at the ventral midline directed by secreted proteins of the netrin family. In the embryonic chick spinal cord netrin-1 mRNA is expressed by floor plate cells and netrin-2 mRNA by neural epithelial cells. Antibodies to the two netrins reveal a gradient of netrin protein directly in the path of commissural axons. The netrin-1 gradient itself extends many cell diameters dorsal to the floor plate, the site of netrin-1 expression. A similar distribution of netrin-1 protein has been detected in embryonic rat and mouse spinal cord. The detection of a gradient of netrin-1 protein supports the operation of long-range chemotropic mechanisms in the developing nervous system.