Nervous system

About: Nervous system is a research topic. Over the lifetime, 16729 publications have been published within this topic receiving 847181 citations.

Absence of the Mid-sized Neurofilament Subunit Decreases Axonal Calibers, Levels of Light Neurofilament (NF-L), and Neurofilament Content

Abstract: Neurofilaments (NFs) are prominent components of large myelinated axons and probably the most abundant of neuronal intermediate filament proteins. Here we show that mice with a null mutation in the mid-sized NF (NF-M) subunit have dramatically decreased levels of light NF (NF-L) and increased levels of heavy NF (NF-H). The calibers of both large and small diameter axons in the central and peripheral nervous systems are diminished. Axons of mutant animals contain fewer neurofilaments and increased numbers of microtubules. Yet the mice lack any overt behavioral phenotype or gross structural defects in the nervous system. These studies suggest that the NF-M subunit is a major regulator of the level of NF-L and that its presence is required to achieve maximal axonal diameter in all size classes of myelinated axons.

Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons.

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.

Pain mechanisms and management: a central perspective.

Abstract: Although pain is always intense and unpleasant, the capacity to experience this sensation is, under normal circumstances, fundamental to the preservation of bodily integrity. Clinically, however, after injury to peripheral tissue or directly to the nervous system, spontaneous and evoked pain manifest that serve no physiologic function, are crippling to patients, and are difficult to treat. Here, we review the specific role of the dorsal horn of the spinal cord in the mechanisms of nociceptive protective pain and the spinal plasticity that occurs after nerve and tissue injury. This spinal neuronal plasticity is shown to be a key contributor to pathologic pain hypersensitivity. The potential for the molecular mechanisms responsible for the spinal plasticity in revealing new targets for future treatment is also discussed.

Multiple Actions of Pituitary Adenylyl Cyclase Activating Peptide in Nervous System Development and Regeneration

Abstract: Pituitary adenylyl cyclase activating peptide (PACAP) is widely expressed in the embryonic brain at the onset of neurogenesis, and is strongly upregulated in several models of nerve injury. Moreover, high-affinity PACAP receptors are expressed in proliferative zones in the embryonic and postnatal nervous system suggesting that PACAP regulates the development of both neuronal and glial precursors. Tissue culture studies indicate that PACAP exerts a variety of growth factor-like actions that depend on the origin of the cell population and developmental stage. These effects include regulation of proliferation, survival, maturation, neurite outgrowth, and expression of trophic factors, cytokines and trk receptors. The presence of other growth factors can also markedly affect these actions of PACAP, for example, reversing PACAP's effect from proliferative to antiproliferative. In vivo models now provide additional evidence that PACAP acts in neural development and regeneration.

Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems.

Abstract: Constitutive activation of the Notch pathway can promote gliogenesis by peripheral (PNS) and central (CNS) nervous system progenitors. This raises the question of whether physiological Notch signaling regulates gliogenesis in vivo. To test this, we conditionally deleted Rbpsuh (Rbpj) from mouse PNS or CNS progenitors using Wnt1-Cre or Nestin-Cre. Rbpsuh encodes a DNA-binding protein (RBP/J) that is required for canonical signaling by all Notch receptors. In most regions of the developing PNS and spinal cord, Rbpsuh deletion caused only mild defects in neurogenesis, but severe defects in gliogenesis. These resulted from defects in glial specification or differentiation, not premature depletion of neural progenitors, because we were able to culture undifferentiated progenitors from the PNS and spinal cord despite their failure to form glia in vivo. In spinal cord progenitors, Rbpsuh was required to maintain Sox9 expression during gliogenesis, demonstrating that Notch signaling promotes the expression of a glial-specification gene. These results demonstrate that physiological Notch signaling is required for gliogenesis in vivo, independent of the role of Notch in the maintenance of undifferentiated neural progenitors.