microRNA-222 targeting PTEN promotes neurite outgrowth from adult dorsal root ganglion neurons following sciatic nerve transection.

Dorsal root ganglia (DRG) neurons spontaneously undergo neurite growth after nerve injury. MicroRNAs (miRNAs), as small, non-coding RNAs, negatively regulate gene expression in a variety of biological processes. The roles of miRNAs in the regulation of responses of DRG neurons to injury stimuli, however, are not fully understood.

Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves.

Crush injury or axotomy of peripheral nerves results in the rapid production of the inflammatory cytokines, which were confirmed in various models, to some extent, to be noxious to the myelin sheath or Schwann cells (SCs). TNF-α is one of the primary initiators of the inflammatory cascade and exerts pleiotropic functions in the physiological conditions by binding to its receptors, type I (TNFRI) and type II (TNFRII). The pathway molecules TNFRI, Birc2 and Birc3 play key roles during the activation of the signaling.

Involvement of gecko SNAP25b in spinal cord regeneration by promoting outgrowth and elongation of neurites.

SNARE complex mediates cellular membrane fusion events essential for neurotransmitter release and synaptogenesis. SNAP25, a member of the SNARE proteins, plays critical roles during the development of the central nervous system via regulation by alternative splicing and protein kinase phosphorylation. To date, little information is available regarding the protein in the spinal cord regeneration, especially for the postnatal highly expressed isoform SNAP25b.

Antiaging effects of simvastatin on vascular endothelial cells.

The anti-inflammatory, antioxidative, and antiarteriosclerosis activities of simvastatin along with its protective effects on the endothelium suggest that it may also have antiaging effects. The aim of this study was to investigate the antiaging effects of simvastatin as well as its effects on sirtuin 1 (SIRT1) expression in endothelial cells. Aged rats and human umbilical vein endothelial cells were treated with simvastatin in the presence and absence of oxidized low-density lipoprotein (OX-LDL).

miR-182 inhibits Schwann cell proliferation and migration by targeting FGF9 and NTM, respectively at an early stage following sciatic nerve injury.

The regulation of Schwann cell (SC) responses to injury stimuli by microRNAs (miRNAs) remains to be explored. Here, we identified 17 miRNAs that showed dynamic expression alterations at five early time points following rat sciatic nerve resection. Then we analyzed the expression pattern of 17 miRNAs, and integrated their putative targets with differentially expressed mRNAs.

The influence of substrate stiffness on the behavior and functions of Schwann cells in culture.

Solid tissues in the body possess a range of stiffness and provide cells with an instructive microenvironment. Scaffolds in tissue engineering should be rationally designed to become an adhesion substrate friendly to cells. Schwann cells are the principal glial cell in the peripheral nervous system and used as support cells for generating tissue-engineered nerve grafts.

Gene expression profiling of the rat sciatic nerve in early Wallerian degeneration after injury.

Wallerian degeneration is an important area of research in modern neuroscience. A large number of genes are differentially regulated in the various stages of Wallerian degeneration, especially during the early response. In this study, we analyzed gene expression in early Wallerian degeneration of the distal nerve stump at 0, 0.

Comparative proteomic analysis of differentially expressed proteins between peripheral sensory and motor nerves.

Peripheral sensory and motor nerves have different functions and different approaches to regeneration, especially their distinct ability to accurately reinervate terminal nerve pathways. To understand the molecular aspects underlying these differences, the proteomics technique by coupling isobaric tags for relative and absolute quantitation (iTRAQ) with online two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) was used to investigate the protein profile of sensory and motor nerve samples from rats. A total of 1472 proteins were identified in either sensory or motor nerve.

Comparative proteomic analysis of primary schwann cells and a spontaneously immortalized schwann cell line RSC 96: a comprehensive overview with a focus on cell adhesion and migration related proteins.

Schwann cells (SCs) are the principal glial cells of the peripheral nervous system (PNS). As a result of tissue heterogeneity and difficulties in the isolation and culture of primary SCs, a considerable understanding of SC biology is obtained from SC lines. However, the differences between the primary SCs and SC lines remain uncertain.

The expression changes of Numblike in rat brain cortex after traumatic brain injury.

Numblike (Numbl) plays an important role in ependymal wall integrity and subventricular zone neuroblast survival. And Numbl is specifically expressed in the brain. However, its expression and function in the central nervous system lesion are still unclear.

A proteome map of primary cultured rat Schwann cells.

Background: Schwann cells (SCs) are the principal glial cells of the peripheral nervous system with a wide range of biological functions. SCs play a key role in peripheral nerve regeneration and are involved in several hereditary peripheral neuropathies. The objective of this study was to gain new insight into the whole protein composition of SCs.

The cloning of growth associated protein 43 of Gekko japonicus and its effect on cell morphology.

The growth-associated protein 43 (GAP-43) gene of Gekko japonicus was obtained from a brain and spinal cord cDNA library. The results of northern blot analysis showed the gecko GAP-43 gene transcript is 1.7 kb in length, and it was abundantly expressed in tissues of brain, spinal cord and ovary.

Identification and functional analysis of novel micro-RNAs in rat dorsal root ganglia after sciatic nerve resection.

Peripheral nerve injures are quite common in clinical practice, and many studies have tried to explore the underlying molecular mechanisms. This study focuses on the identification and functional analysis of novel miRNAs in rat dorsal root ganglia (DRGs) following sciatic nerve resection, which is a classic model for studying peripheral nerve injury and regeneration. By using Solexa sequencing, computational analysis, Q-PCR verification, and Dicer knockdown assay, 114 novel miRNAs in rats were identified, of which 51 novel miRNAs were first reported in rat DRGs, and 63 novel miRNAs were produced at days 1, 4, 7, and 14 following sciatic nerve resection.

miR-221 and miR-222 promote Schwann cell proliferation and migration by targeting LASS2 after sciatic nerve injury.

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Their roles in regulating the responses of Schwann cells (SCs) to injury stimuli remain unexplored. Here we report dynamic alteration of miRNA expression following rat sciatic nerve injury using microarray analysis.

Bridging peripheral nerve defects with a tissue engineered nerve graft composed of an in vitro cultured nerve equivalent and a silk fibroin-based scaffold.

Tissue engineered nerve grafts are considered as a promising alternative to autologous nerve grafts used for peripheral nerve repair. The differences between these two types of nerve grafts are mainly in the regenerative microenvironment established by them. To construct ideal tissue engineered nerve grafts, it is therefore required to develop a better way to introduce biochemical cues into a neural scaffold, as compared to single or combined use of support cells and growth factors.

Laser doppler perfusion imaging of skin territory to reflect autonomic functional recovery following sciatic nerve autografting repair in rats.

Peripheral nerve repair requires comprehensive evaluation of functional outcomes of nerve regeneration; however, autonomic nerve function is seldom evaluated probably due to lack of suitable quantitative methods. This study sought to determine whether autonomic functional recovery could be reflected by cold-induced vasodilation (CIVD) within target skin territory, as monitored by laser Doppler perfusion imaging (LDPI). Rats with sciatic nerve defect injury received autologous nerve grafting, and the plantar surface of the hind feet was subjected to LDPI analysis following nerve repair.

Inhibition of gecko GSK-3β promotes elongation of neurites and oligodendrocyte processes but decreases the proliferation of blastemal cells.

GSK-3β signaling is involved in regulation of both neuronal and glial cell functions, and interference of the signaling affects central nervous system (CNS) development and regeneration. Thus, GSK-3β was proposed to be an important therapeutic target for promoting functional recovery of adult CNS injuries. To further clarify the regulatory function of the kinase on the CNS regeneration, we characterized gecko GSK-3β and determined the effects of GSK-3β inactivation on the neuronal and glial cell lines, as well as on the gecko tail (including spinal cord) regeneration.

iTRAQ-coupled 2D LC-MS/MS analysis on differentially expressed proteins in denervated tibialis anterior muscle of Rattus norvegicus.

To understand the molecular aspects of denervation-induced atrophy of skeletal muscles, isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry were performed to detect a total of 260 proteins that were differentially expressed in the rat tibialis anterior muscle at different times (1, 4, and 8 weeks) after rat sciatic nerve transection. Western blot, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were further conducted for protein validation, functional annotation, and pathway identification, respectively. Among 260 dysregulated proteins, metabolic enzymes represented the largest class of proteins differentially expressed; a down-regulation of β-enolase might be associated with a decreased expression of fast-twitch myosin-4; the 14-3-3 proteins displayed an up-regulation, which might facilitate the inhibition of mTOR signaling; an up-regulation of α-crystallin B chain might be related to the later onset and the slower progress of atrophy; an up-regulation of phosphatidylethanolamine-binding protein-1 perhaps progressively abrogated the cell survival and antiapoptotic properties during muscle atrophy.

Lysosomal exocytosis in Schwann cells contributes to axon remyelination.

Myelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein P0, which accounts for over half the total protein of compact myelin in the peripheral nervous system and exhibit Ca(2+) -dependent exocytosis in response to various stimuli.

Joint use of a chitosan/PLGA scaffold and MSCs to bridge an extra large gap in dog sciatic nerve.

Background: Tissue-engineered nerve grafts (TENGs) constitute a promising alternative to nerve autografts that are recognized as the gold standard for surgical repair of peripheral nerve gaps.

Objective: To investigate the feasibility of using TENGs for bridging extra large peripheral nerve gaps in large animals.

Methods: TENGs were constructed by incorporating autologous bone marrow mesenchymal stem cells (MSCs) into a neural scaffold that consisted of a chitosan conduit inserted with poly(lactic-co-glycolic acid) (PLGA) fibers.

Profile of microRNAs following rat sciatic nerve injury by deep sequencing: implication for mechanisms of nerve regeneration.

Unlike the central nervous system, peripheral nerves can regenerate when damaged. MicroRNA (miRNA) is a novel class of small, non-coding RNA that regulates gene expression at the post-transcriptional level. Here, we report regular alterations of miRNA expression following rat sciatic nerve injury using deep sequencing.

Identification and functional annotation of novel microRNAs in the proximal sciatic nerve after sciatic nerve transection.

The peripheral nervous system is able to regenerate after injury, and regeneration is associated with the expression of many genes and proteins. MicroRNAs are evolutionarily conserved, small, non-coding RNA molecules that regulate gene expression at the level of translation. In this paper, we focus on the identification and functional annotation of novel microRNAs in the proximal sciatic nerve after rat sciatic nerve transection.

Altered microRNA expression following sciatic nerve resection in dorsal root ganglia of rats.

MicroRNAs (miRNAs) are a class of small, non-coding RNAs (∼22 nucleotides) that negatively regulate gene expression post-transcriptionally, either through translational inhibition or degradation of target mRNAs. We uncovered a previously unknown alteration in the expression of miRNAs in the dorsal root ganglia (DRG) at 1, 4, 7, and 14 days after resection of the sciatic nerve in rats using microarray analysis. Thirty-two significantly upregulated and 18 downregulated miRNAs were identified in the DRG at four time points following sciatic nerve injury.

Age-related changes in myelin morphology, electrophysiological property and myelin-associated protein expression of mouse sciatic nerves.

This study investigated the morphological and functional changes in peripheral nerves during the maturation and aging process. In a mouse sciatic nerve model, electron micrographs revealed that the number of myelin sheath lamellae gradually increased from 1 week through 12 months of age, when it reached the peak value, and then remained unchanged until 18 months of age; electrophysiological examinations showed that the amplitude of compound muscle action potentials gradually increased from 1 week through 18 months of age and displayed a positive linear correlation with the number of myelin sheath lamellae. Western blot analysis exhibited the age-related expression patterns of four myelin-associated proteins, i.

Elevated plasma levels of adropin in heart failure patients.

Background: Recent studies have suggested that a higher body mass index (BMI) is associated with an improved prognosis in heart failure (HF). Adropin is a recently identified protein that has been implicated in the maintenance of energy homeostasis. In the present study, we investigated plasma adropin levels in patients with HF and evaluated the relationship between the levels and the severity of HF.