Neural Stem Cells, Excited

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (Impact Factor: 33.61). 03/2013; 339(6127):1534-5. DOI: 10.1126/science.1237576
Source: PubMed


Electrical activity in the adult mammalian brain triggers neurogenesis.

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    ABSTRACT: The aim of the present study is to clarify the functional expression and physiological role in neural progenitor cells (NPCs) of carnitine/organic cation transporter OCTN1/SLC22A4, which accepts the naturally occurring food-derived antioxidant ergothioneine (ERGO) as a substrate in vivo. Real-time PCR analysis revealed that mRNA expression of OCTN1 was much higher than that of other organic cation transporters in mouse cultured cortical NPCs. Immunocytochemical analysis showed colocalization of OCTN1 with the NPC marker nestin in cultured NPCs and mouse embryonic carcinoma P19 cells differentiated into neural progenitor-like cells (P19-NPCs). These cells exhibited time-dependent [(3)H]ERGO uptake. These results demonstrate that OCTN1 is functionally expressed in murine NPCs. Cultured NPCs and P19-NPCs formed neurospheres from clusters of proliferating cells in a culture time-dependent manner. Exposure of cultured NPCs to ERGO or other antioxidants (edaravone and ascorbic acid) led to a significant decrease in the area of neurospheres with concomitant elimination of intracellular reactive oxygen species. Transfection of P19-NPCs with small interfering RNA for OCTN1 markedly promoted formation of neurospheres with a concomitant decrease of [(3)H]ERGO uptake. On the other hand, exposure of cultured NPCs to ERGO markedly increased the number of cells immunoreactive for the neuronal marker βIII-tubulin, but decreased the number immunoreactive for the astroglial marker glial fibrillary acidic protein (GFAP), with concomitant up-regulation of neuronal differentiation activator gene Math1. Interestingly, edaravone and ascorbic acid did not affect such differentiation of NPCs, in contrast to the case of proliferation. Knockdown of OCTN1 increased the number of cells immunoreactive for GFAP, but decreased the number immunoreactive for βIII-tubulin, with concomitant down-regulation of Math1 in P19-NPCs. Thus, OCTN1-mediated uptake of ERGO in NPCs inhibits cellular proliferation via regulation of oxidative stress, and also promotes cellular differentiation by modulating the expression of basic helix-loop-helix transcription factors via an unidentified mechanism different from antioxidant action.
    PLoS ONE 02/2014; 9(2):e89434. DOI:10.1371/journal.pone.0089434 · 3.23 Impact Factor
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    ABSTRACT: Neural stem cells in the adult mammalian hippocampus continuously generate new functional neurons, which modify the hippocampal network and significantly contribute to cognitive processes and mood regulation. Here, we show that the development of new neurons from stem cells in adult mice is paralleled by extensive changes to mitochondrial mass, distribution, and shape. Moreover, exercise-a strong modifier of adult hippocampal neurogenesis-accelerates neuronal maturation and induces a profound increase in mitochondrial content and the presence of mitochondria in dendritic segments. Genetic inhibition of the activity of the mitochondrial fission factor dynamin-related protein 1 (Drp1) inhibits neurogenesis under basal and exercise conditions. Conversely, enhanced Drp1 activity furthers exercise-induced acceleration of neuronal maturation. Collectively, these results indicate that adult hippocampal neurogenesis requires adaptation of the mitochondrial compartment and suggest that mitochondria are targets for enhancing neurogenesis-dependent hippocampal plasticity.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 05/2014; 34(19):6624-33. DOI:10.1523/JNEUROSCI.4972-13.2014 · 6.34 Impact Factor
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    ABSTRACT: Background: Infantile cerebral palsy (ICP) is currently one of the major diseases that cause paralysis and mental retardation in children. The stem cell treatment is a promising alternative for this disease. Material and method: Twenty-eight patients with ICP and epilepsy (12 cases) since 4.5 to 24 years received omental transplantation on the carotid bifurcation, anterior perforated space (APS), optic chiasm, and the temporal lobes. During surgery we found: 1) small and thin omentum in 13 cases, 2) adhesive arachnoiditis in the chiasmatic cistern and surrounding areas in 18 cases, 3) ischemic microinfarcts and atrophy in the surgical area; 4) vascular anomalies in the anterior perforating arteries; 5) several collapsed and exsanguinated perforating arteries,and 6) arachnoid cyst in 3 cases. Of all patients, thirteen cases received only, omentum on the APS, because the omentum was small. Results: Neurological improvement occurred since the first days after surgery in 21 patients. The epileptic seizures were reduced or aborted. Currently, 10 to 26 months after the operation, the patients have improved in different degrees. Likewise, the clinical data in 10 patients with minimal brain dysfunction were reversed. Conclusions: These results indicate that omental transplantation against ICP is effective. Because the omentum provoke revascularization and provide mesenchymal stem cells to the injured area, Moreover, the omentum favors the proliferation and migration of neural stem cells from the subventricular zone of the adult human brain.