Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against H2O2-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert ω-6 to ω-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H2O2 as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that ω-3 PUFAs resist oxidative injury to NPCs

Generation of integration-free neural progenitor cells from cells in human urine

Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.postprin

Soluble NgR Fusion Protein Modulates the Proliferation of Neural Progenitor Cells via the Notch Pathway

NogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expression of nestin, βIII-Tubulin, GFAP and Nogo-A on these cells was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition, we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation. Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway

Transplantation of neural stem cells for motoneuron degeneration due to axonal injury

published_or_final_versionAnatomyDoctoralDoctor of Philosoph

Numerical study on the hydrodynamics of thunniform bio-inspired swimming under self-propulsion

<div><p>Numerical simulations are employed to study the hydrodynamics of self-propelled thunniform swimming. The swimmer is modeled as a tuna-like flexible body undulating with kinematics of thunniform type. The wake evolution follows the vortex structures arranged nearly vertical to the forward direction, vortex dipole formation resulting in the propulsion motion, and finally a reverse Kármán vortex street. We also carry out a systematic parametric study of various aspects of the fluid dynamics behind the freely swimming behavior, including the swimming speed, hydrodynamic forces, power requirement and wake vortices. The present results show that the fin thrust as well as swimming velocity is an increasing function of both tail undulating amplitude <i>A</i>_<i>p</i> and oscillating amplitude of the caudal fin <i>θ</i>_<i>m</i>. Whereas change on the propulsive performance with <i>A</i>_<i>p</i> is associated with the strength of wake vortices and the area of suction region on the fin, the swimming performance improves with <i>θ</i>_<i>m</i> due to the favorable tilting of the fin that make the pressure difference force more oriented toward the thrust direction. Moreover, the energy loss in the transverse direction and the power requirement increase with <i>A</i>_<i>p</i> but decrease with <i>θ</i>_<i>m</i>, and this indicates that for achieving a desired swimming speed increasing <i>θ</i>_<i>m</i> seems more efficiently than increasing <i>A</i>_<i>p</i>. Furthermore, we have compared the current simulations with the published experimental studies on undulatory swimming. Comparisons show that our work tackles the flow regime of natural thunniform swimmers and follows the principal scaling law of undulatory locomotion reported. Finally, this study enables a detailed quantitative analysis, which is difficult to obtain by experiments, of the force production of the thunniform mode as well as its connection to the self-propelled swimming kinematics and vortex wake structure. The current findings help provide insights into the swimming performance and mechanisms of self-propelled thunniform locomotion.</p></div

Vorticity contours at four instants in one period for different oscillating amplitudes of the caudal fin.

<p>For all these cases, <i>A</i>_<i>p</i>/<i>C</i> = 0.6 and <i>f</i> = 1.0Hz. (a) <i>θ</i>_<i>m</i> = 15° and (b) <i>θ</i>_<i>m</i> = 35°.</p

Variation in (a) forward velocity and (b) longitudinal force with time for various <i>A</i>_<i>p</i>.

<p>For all these cases, <i>θ</i>_<i>m</i> = 25° and <i>f</i> = 1.0Hz.</p

Pressure contours on the fish body and selected sectional planes at four instants during one specific cycle at the cruising stage.

<p>The color scheme for pressure contours is such that red colors denote the highest pressure and blue the lowest pressure.</p

The midlines of the flexible, undulating body during one period.

<p>Since the front part of the swimmer makes no undulation, only the rear is shown. The red line shows the motion trajectory of the tail peduncle end.</p