Showing papers on "Nervous system published in 2010"
TL;DR: Cell biology and mouse genetics have provided insight into axon–glia signalling and the molecular architecture of the myelin sheath, and glial cells that myelinate axons were found to have a dual role by also supporting the long-term integrity of those axons.
Abstract: The myelination of axons by glial cells was the last major step in the evolution of cells in the vertebrate nervous system, and white-matter tracts are key to the architecture of the mammalian brain. Cell biology and mouse genetics have provided insight into axon–glia signalling and the molecular architecture of the myelin sheath. Glial cells that myelinate axons were found to have a dual role by also supporting the long-term integrity of those axons. This function may be independent of myelin itself. Myelin abnormalities cause a number of neurological diseases, and may also contribute to complex neuropsychiatric disorders.
907 citations
TL;DR: The latest insights into the function of Wnt signalling in the adult nervous system and therapeutic opportunities for neurodegenerative diseases such as Alzheimer's and Parkinson's disease are discussed.
Abstract: The roles of the Wnt signalling pathway in several developmental processes, including synaptic differentiation, are well characterized. The expression of Wnt ligands and Wnt signalling components in the mature mammalian CNS suggests that this pathway might also play a part in synaptic maintenance and function. In fact, Wnts have a crucial role in synaptic physiology, as they modulate the synaptic vesicle cycle, the trafficking of neurotransmitter receptors and the interaction of these receptors with scaffold proteins in postsynaptic regions. In addition, Wnts participate in adult neurogenesis and protect excitatory synaptic terminals from amyloid-β oligomer toxicity. Here, the latest insights into the function of Wnt signalling in the adult nervous system and therapeutic opportunities for neurodegenerative diseases such as Alzheimer's and Parkinson's disease are discussed.
574 citations
TL;DR: This review will critically examine the role of the immune system in modulating chronic pain in animal models of nervous system injury, and highlight the possible therapeutic opportunities to intervene in the development and maintenance of neuropathic pain.
510 citations
TL;DR: Evidence has accumulated that suggests heterogeneity of astrocytes across brain regions as well as within the same brain regions, which will greatly aid investigation of the function of astracytes in normal brain aswell as the roles of astrospecies in neurological disorders.
492 citations
TL;DR: It is reported that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system.
Abstract: In patients with Parkinson's disease (PD), the associated pathology follows a characteristic pattern involving inter alia the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the substantia nigra, providing the basis for the neuropathological staging of the disease. Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce alpha-synuclein accumulation in all the above-mentioned nervous system structures of wild-type mice. Moreover, we also observed inflammation and alpha-synuclein phosphorylation in the ENS and DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I measurements showed no systemic Complex I inhibition after 1.5 months of treatment. These alterations are sequential, appearing only in synaptically connected nervous structures, treatment time-dependent and accompanied by inflammatory signs and motor dysfunctions. These results strongly suggest that the local effect of pesticides on the ENS might be sufficient to induce PD-like progression and to reproduce the neuroanatomical and neurochemical features of PD staging. It provides new insight into how environmental factors could trigger PD and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system.
456 citations
TL;DR: These findings provide the first evidence that DAGLα is the major biosynthetic enzyme for 2-AG in the nervous system and reveal an essential role for this enzyme in regulating retrograde synaptic plasticity and adult neurogenesis.
Abstract: Endocannabinoids (eCBs) function as retrograde signaling molecules at synapses throughout the brain, regulate axonal growth and guidance during development, and drive adult neurogenesis. There remains a lack of genetic evidence as to the identity of the enzyme(s) responsible for the synthesis of eCBs in the brain. Diacylglycerol lipase-alpha (DAGLalpha) and -beta (DAGLbeta) synthesize 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain. However, their respective contribution to this and to eCB signaling has not been tested. In the present study, we show approximately 80% reductions in 2-AG levels in the brain and spinal cord in DAGLalpha(-/-) mice and a 50% reduction in the brain in DAGLbeta(-/-) mice. In contrast, DAGLbeta plays a more important role than DAGLalpha in regulating 2-AG levels in the liver, with a 90% reduction seen in DAGLbeta(-/-) mice. Levels of arachidonic acid decrease in parallel with 2-AG, suggesting that DAGL activity controls the steady-state levels of both lipids. In the hippocampus, the postsynaptic release of an eCB results in the transient suppression of GABA-mediated transmission at inhibitory synapses; we now show that this form of synaptic plasticity is completely lost in DAGLalpha(-/-) animals and relatively unaffected in DAGLbeta(-/-) animals. Finally, we show that the control of adult neurogenesis in the hippocampus and subventricular zone is compromised in the DAGLalpha(-/-) and/or DAGLbeta(-/-) mice. These findings provide the first evidence that DAGLalpha is the major biosynthetic enzyme for 2-AG in the nervous system and reveal an essential role for this enzyme in regulating retrograde synaptic plasticity and adult neurogenesis.
418 citations
TL;DR: Findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.
Abstract: Although axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed behavioral, electrophysiological and anatomical adaptations. We found marked spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.
364 citations
TL;DR: This neural pathway suggests a means by which a single pheromone can elicit different behaviours in the two sexes, and is identified as a male-specific neuropil that integrates inputs from multiple sensory systems and sends outputs to the ventral nerve cord.
Abstract: Innate differences between male and female behaviours must be inscribed in their respective genomes, but how these encode distinct neuronal circuits remains largely unknown. Focusing on sex-specific responses to the cVA pheromone in fruitflies, Richard Axel and colleagues have now identified a chain of four successive neurons carrying olfactory signals down to motor centres, with all male-to-female anatomical differences lying downstream of a conserved sensory cell. The techniques developed by the team should help others in the task of neuronal circuit mapping, which remains daunting even for the relatively simple fly brain. Innate differences between male and female behaviours must be inscribed in their respective genomes, but how these encode distinct neuronal circuits remains largely unclear. Focusing on sex specific responses to the cVA pheromone in fruitflies, a chain of four successive neurons carrying olfactory signals down to motor centres has been identified, with all male to female anatomical differences lying downstream of a conserved sensory cell. The techniques developed should help others in the task of neuronal circuit mapping, which remains daunting even for the relatively simple fly brain. Drosophila show innate olfactory-driven behaviours that are observed in naive animals without previous learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically programmed. Despite the numerical simplicity of the fly nervous system, features of the anatomical organization of the fly brain often confound the delineation of these circuits. Here we identify a neural circuit responsive to cVA, a pheromone that elicits sexually dimorphic behaviours1,2,3,4. We have combined neural tracing using an improved photoactivatable green fluorescent protein (PA-GFP) with electrophysiology, optical imaging and laser-mediated microlesioning to map this circuit from the activation of sensory neurons in the antennae to the excitation of descending neurons in the ventral nerve cord. This circuit is concise and minimally comprises four neurons, connected by three synapses. Three of these neurons are overtly dimorphic and identify a male-specific neuropil that integrates inputs from multiple sensory systems and sends outputs to the ventral nerve cord. This neural pathway suggests a means by which a single pheromone can elicit different behaviours in the two sexes.
325 citations
TL;DR: It is shown that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS) on peripheral infection with vesicular stomatitis virus.
Abstract: Lymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7-10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection.
301 citations
TL;DR: In this article, a review traces new efforts to characterize and control toll-like receptor 4 in inflammatory etiologies of the nervous system, showing that an important contributor to microglial activation is a pathogenassociated molecular pattern receptor known to initiate an inflammatory cascade in response to various CNS stimuli.
Abstract: The responses of the brain to infection, ischemia and trauma share remarkable similarities. These and other conditions of the CNS coordinate an innate immune response marked by activation of microglia, the macrophage-like cells of the nervous system. An important contributor to microglial activation is toll-like receptor 4, a pathogen-associated molecular pattern receptor known to initiate an inflammatory cascade in response to various CNS stimuli. The present review traces new efforts to characterize and control toll-like receptor 4 in inflammatory etiologies of the nervous system.
297 citations
TL;DR: Targeting ASIC channels at different levels of the nervous system could therefore be an interesting strategy for the relief of pain.
TL;DR: Current evidence that supports the notion that astrocytes are integral components of nervous system networks are summarized and some functional properties of intercellular signalling in neuron–glia networks are discussed.
Abstract: Numerous evidence demonstrates that astrocytes, a type of glial cell, are integral functional elements of the synapses, responding to neuronal activity and regulating synaptic transmission and plasticity. Consequently, they are actively involved in the processing, transfer and storage of information by the nervous system, which challenges the accepted paradigm that brain function results exclusively from neuronal network activity, and suggests that nervous system function actually arises from the activity of neuron–glia networks. Most of our knowledge of the properties and physiological consequences of the bidirectional communication between astrocytes and neurons resides at cellular and molecular levels. In contrast, much less is known at higher level of complexity, i.e. networks of cells, and the actual impact of astrocytes in the neuronal network function remains largely unexplored. In the present article, we summarize the current evidence that supports the notion that astrocytes are integral components of nervous system networks and we discuss some functional properties of intercellular signalling in neuron–glia networks.
TL;DR: Even though further work is needed to understand the various roles of VEGF in the nervous system and to distinguish direct neuronal effects from indirect, vessel-mediated effects, V EGF can be considered a promising tool to promote neuronal health and nerve repair.
Abstract: Vascular endothelial growth factor (VEGF, VEGFA) is critical for blood vessel growth in the developing and adult nervous system of vertebrates. Several recent studies demonstrate that VEGF also promotes neurogenesis, neuronal patterning, neuroprotection and glial growth. For example, VEGF treatment of cultured neurons enhances survival and neurite growth independently of blood vessels. Moreover, evidence is emerging that VEGF guides neuronal migration in the embryonic brain and supports axonal and arterial co-patterning in the developing skin. Even though further work is needed to understand the various roles of VEGF in the nervous system and to distinguish direct neuronal effects from indirect, vessel-mediated effects, VEGF can be considered a promising tool to promote neuronal health and nerve repair.
TL;DR: Evidence is given for bidirectional communication between brain and WAT occurring via the sympathetic nervous system (SNS) and sensory innervation of this tissue and a possible neural negative feedback loop to regulate lipolysis.
TL;DR: Transgenic mice expressing mutant alpha-synuclein (either A53T or A30P) from insertions of an entire human SNCA gene are developed as models for the familial disease and recapitulate the early gastrointestinal abnormalities seen in human PD.
Abstract: Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is familial. Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes α-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD. We set out to develop transgenic mice expressing mutant α-synuclein (either A53T or A30P) from insertions of an entire human SNCA gene as models for the familial disease. Both the A53T and A30P lines show robust abnormalities in enteric nervous system (ENS) function and synuclein-immunoreactive aggregates in ENS ganglia by 3 months of age. The A53T line also has abnormal motor behavior but neither demonstrates cardiac autonomic abnormalities, olfactory dysfunction, dopaminergic neurotransmitter deficits, Lewy body inclusions or neurodegeneration. These animals recapitulate the early gastrointestinal abnormalities seen in human PD. The animals also serve as an in vivo system in which to investigate therapies for reversing the neurological dysfunction that target α-synuclein toxicity at its earliest stages.
TL;DR: Novel findings on the key processes that govern the cell biology of migrating neurons are summarized, describing recent advances in their molecular regulation in different migratory pathways of the brain, spinal cord, and peripheral nervous system.
TL;DR: Astrocytes have been revealed as integral elements involved in the synaptic physiology, therefore contributing to the processing, transfer and storage of information by the nervous system.
TL;DR: These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD) and schizophrenia.
Abstract: Although the brain has classically been considered “immune-privileged”, current research suggests an extensive communication between the immune and nervous systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased central nervous system (CNS). Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system – specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of geniculate, cortical and hippocampal synapses, and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD) and schizophrenia.
TL;DR: Compartmentalized Campenot cell culture chambers are employed to obtain a pure axonal RNA fraction of superior cervical ganglia neurons, and the miRNA expression levels in these subcellular structural domains are determined by microarray analysis and by real-time reverse-transcription polymerase chain reaction.
Abstract: microRNAs (miRNAs) constitute a novel class of small, noncoding RNAs that act as negative post-transcriptional regulators of gene expression. Although the nervous system is a prominent site of miRNA expression, little is known about the spatial expression profiles of miRNAs in neurons. Here, we employed compartmentalized Campenot cell culture chambers to obtain a pure axonal RNA fraction of superior cervical ganglia (SCG) neurons, and determined the miRNA expression levels in these subcellular structural domains by microarray analysis and by real-time reverse-transcription polymerase chain reaction. The data revealed stable expression of a number of mature miRNAs that were enriched in the axons and presynaptic nerve terminals. Among the 130 miRNAs identified in the axon, miR-15b, miR-16, miR-204, and miR-221 were found to be highly abundant in distal axons as compared with the cell bodies of primary sympathetic neurons. Moreover, a number of miRNAs encoded by a common primary transcript (pri-miRNA) were differentially expressed in the distal axons, suggesting that there is a differential subcellular transport of miRNAs derived from the same coding region of the genome. Taken together, the data provide an important resource for future studies on the regulation of axonal protein synthesis and the role played by miRNAs in the maintenance of axonal structure and function as well as neuronal growth and development.
TL;DR: Although cG MP production appears to mediate the physiological signaling by NO, the specific roles of cGMP-dependent ion channels, protein kinases and phosphodiesterases in mediating NO action remain to be determined.
TL;DR: The role of glial calcium signalling in various forms of pathological processes including neurological and psychiatric disorders and neurodegeneration is summarised.
TL;DR: Emerging evidence for a novel transmembrane mechanism for ligand‐specific p75NTR activation and several mechanisms by which p 75NTR‐dependent apoptotic and nonapoptotic responses can be selective activated are reviewed.
Abstract: Neurotrophins are initially synthesized as larger precursors (proneurotrophins), which undergo proteolytic cleavage to yield mature forms. Although the functions of the mature neurotrophins have been well established during neural development and in the adult nervous system, roles for the proneurotrophins in developmental and injury-induced cell death, as well as in synaptic plasticity, have only recently been appreciated. Interestingly, both mature neurotrophins and proneurotrophins utilize dual-receptor complexes to mediate their actions. The mature neurotrophin coreceptors consist of the Trk receptor tyrosine kinases and p75NTR, wherein Trk transduces survival and differentiative signaling, and p75NTR modulates the affinity and selectivity of Trk activation. On the other hand, proneurotrophins engage p75NTR and the structurally distinct coreceptor sortilin, to initiate p75NTR-dependent signal transduction cascade. Although the specificity of mature neurotrophins vs. proneurotrophins actions is due in part to the formation of distinct coreceptor complexes, a number of recent studies highlight how different p75NTR-mediated cellular actions are modulated. Here, we review emerging evidence for a novel transmembrane mechanism for ligand-specific p75NTR activation and several mechanisms by which p75NTR-dependent apoptotic and nonapoptotic responses can be selective activated. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010
TL;DR: The history, recent discoveries, and unanswered questions surrounding the relationship between the vascular and nervous systems are explored with a focus on developmental signaling cues that guide network formation and establish the interface between these two systems.
Abstract: The vascular and nervous systems share a common necessity of circuit formation to coordinate nutrient and information transfer, respectively. Shared developmental principles have evolved to orchestrate the formation of both the vascular and the nervous systems. This evolution is highlighted by the identification of specific guidance cues that direct both systems to their target tissues. In addition to sharing cellular and molecular signaling events during development, the vascular and nervous systems also form an intricate interface within the central nervous system called the neurovascular unit. Understanding how the neurovascular unit develops and functions, and more specifically how the blood-brain barrier within this unit is established, is of utmost importance. We explore the history, recent discoveries, and unanswered questions surrounding the relationship between the vascular and nervous systems with a focus on developmental signaling cues that guide network formation and establish the interface between these two systems.
TL;DR: The role of extracellular ATP acting through P2X7 receptors as an initiator of a neurotoxic phenotype that leads to astrocyte-mediated motor neuron death in non-transgenic and SOD1G93A astroCytes is studied.
Abstract: During pathology of the nervous system, increased extracellular ATP acts both as a cytotoxic factor and pro-inflammatory mediator through P2X7 receptors. In animal models of amyotrophic lateral sclerosis (ALS), astrocytes expressing superoxide dismutase 1 (SOD1G93A) mutations display a neuroinflammatory phenotype and contribute to disease progression and motor neuron death. Here we studied the role of extracellular ATP acting through P2X7 receptors as an initiator of a neurotoxic phenotype that leads to astrocyte-mediated motor neuron death in non-transgenic and SOD1G93A astrocytes. We evaluated motor neuron survival after co-culture with SOD1G93A or non-transgenic astrocytes pretreated with agents known to modulate ATP release or P2X7 receptor. We also characterized astrocyte proliferation and extracellular ATP degradation. Repeated stimulation by ATP or the P2X7-selective agonist BzATP caused astrocytes to become neurotoxic, inducing death of motor neurons. Involvement of P2X7 receptor was further confirmed by Brilliant blue G inhibition of ATP and BzATP effects. In SOD1G93A astrocyte cultures, pharmacological inhibition of P2X7 receptor or increased extracellular ATP degradation with the enzyme apyrase was sufficient to completely abolish their toxicity towards motor neurons. SOD1G93A astrocytes also displayed increased ATP-dependent proliferation and a basal increase in extracellular ATP degradation. Here we found that P2X7 receptor activation in spinal cord astrocytes initiated a neurotoxic phenotype that leads to motor neuron death. Remarkably, the neurotoxic phenotype of SOD1G93A astrocytes depended upon basal activation the P2X7 receptor. Thus, pharmacological inhibition of P2X7 receptor might reduce neuroinflammation in ALS through astrocytes.
TL;DR: Peripheral ganglia and visceral organs are also involved in polyglutamine diseases and further elucidation and characterization of PNS lesions will have implications for intravital biopsy diagnosis in neurodegenerative proteinopathy, particularly in Parkinson's disease.
Abstract: Involvement of the peripheral nervous system (PNS) is relatively common in some neurodegenerative proteinopathies of the brain and may be pathogenetically and diagnostically important. In Parkinson’s disease, neuronal α-synuclein aggregates are distributed throughout the nervous system, including the central nervous system (CNS), sympathetic ganglia, enteric nervous system, cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin. The pathological process may target the PNS and CNS at the same time. In multiple system atrophy, numerous glial cytoplasmic inclusions composed of filamentous α-synuclein are widely distributed in the CNS, while α-synuclein accumulation is minimal in the sympathetic ganglia and is restricted to neurons. Neurofibrillary tangles can occur in the sympathetic and spinal ganglia in tauopathy, although they appear to develop independently of cerebral Alzheimer’s disease pathology. In amyotrophic lateral sclerosis, neuronal loss with TDP-43-positive neuronal cytoplasmic inclusions in the spinal ganglia is more frequent than previously thought. Peripheral ganglia and visceral organs are also involved in polyglutamine diseases. Further elucidation and characterization of PNS lesions will have implications for intravital biopsy diagnosis in neurodegenerative proteinopathy, particularly in Parkinson’s disease.
TL;DR: It is expected that further investigation to determine how ATP signaling via P2X receptors participates in the pathogenesis of chronic pain will lead to a better understanding of the molecular mechanisms of pathological pain and provide clues for the development of new therapeutic drugs.
TL;DR: It is shown that overexpression of NeuroD1 in the periventricular region in vivo leads to the rapid appearance of cells with morphological and molecular characteristics of mature neurons in the subventricular zone and rostral migratory stream, and suggests a considerable potential of neuroD1 for use in cell-therapeutic approaches in the nervous system.
Abstract: After their generation and specification in periventricular regions, neuronal precursors maintain an immature and migratory state until their arrival in the respective target structures. Only here are terminal differentiation and synaptic integration induced. Although the molecular control of neuronal specification has started to be elucidated, little is known about the factors that control the latest maturation steps. We aimed at identifying factors that induce terminal differentiation during postnatal and adult neurogenesis, thereby focusing on the generation of periglomerular interneurons in the olfactory bulb. We isolated neuronal precursors and mature neurons from the periglomerular neuron lineage and analyzed their gene expression by microarray. We found that expression of the bHLH transcription factor NeuroD1 strikingly coincides with terminal differentiation. Using brain electroporation, we show that overexpression of NeuroD1 in the periventricular region in vivo leads to the rapid appearance of cells with morphological and molecular characteristics of mature neurons in the subventricular zone and rostral migratory stream. Conversely, shRNA-induced knockdown of NeuroD1 inhibits terminal neuronal differentiation. Thus, expression of a single transcription factor is sufficient to induce neuronal differentiation of neural progenitors in regions that normally do not show addition of new neurons. These results suggest a considerable potential of NeuroD1 for use in cell-therapeutic approaches in the nervous system.
TL;DR: The multiple functions in peripheral and central nervous system development also link SoxE proteins to various human diseases and identify these proteins as promising targets of future therapeutic approaches.
TL;DR: The clinical features, diagnosis, and management options for patients with radiation neurotoxicity, including Brachial or lumbosacral plexopathy, are focused on.