The main hypothesis of this project proposes that the region surrounding the central canal in the spinal cord of young turtles is an active neurogenic zone in which Stem/Progenitor (S/P) cells proliferate, giving rise to immature neurons and glial cells. Connected with this hypothesis is the idea that immature neurons differentiate, migrate and integrate into pre-existing spinal circuits. Injuries and degenerative diseases of the spinal cord are among the most devastating ailments affecting many people. Understanding the biology of S/P cells in species that have retained neurogenesis after birth is crucial in order to develop adequate cell- replacement treatments.
The specific aims of this project are: 1) Identification and characterization of S/P cells in the spinal cord of the turtle, 2) to determine the morphological, fine structural, molecular and functional changes taking place during differentiation of newborn neurons from S/P cells, 3) to study the migration of newborn neurons from the central canal to the parenchyma and their subsequent functional integration into spinal circuitry, and 4) to assess the effects of injury on the production and differentiation of S/P cells. This proposal takes advantage of a unique biological model and applies a multidisciplinary approach involving immunocytochemistry, fine structure analysis, time-lapse imaging and electrophysiology. Both in vivo and in vitro preparations will be used. The immature cells characterized at the electrophysiolgical level will be further analyzed with molecular-structural techniques. Putative migratory behavior of immature cells will be investigated in vitro by means of time-lapse imaging of tagged cells. Finally, the modulatory influence of injury on proliferation and differentiation of S/P cells in animals at variable time points after a complete transection of the spinal cord, will be characterized by immunocytochemical, morphological and electrophysiological techniques. The proposed research will provide important information about the generation, maturation and integration of new neurons in mature sensory-motor circuitry. This knowledge is essential to understand basic neurogenic mechanisms that may remain """"""""dormant"""""""" in the mammalian spinal cord but could hopefully be """"""""awakened"""""""" to alleviate spinal cord diseases. ? ?
| Marichal, Nicolás; Fabbiani, Gabriela; Trujillo-Cenóz, Omar et al. (2016) Purinergic signalling in a latent stem cell niche of the rat spinal cord. Purinergic Signal 12:331-41 |
| Trujillo-Cenoz, Omar; Marichal, Nicolas; Rehermann, Maria Ines et al. (2014) The inner lining of the reptilian brain: a heterogeneous cellular mosaic. Glia 62:300-16 |
| García, Gabriela; Libisch, Gabriela; Trujillo-Cenóz, Omar et al. (2012) Modulation of gene expression during early stages of reconnection of the turtle spinal cord. J Neurochem 121:996-1006 |
| Marichal, Nicolas; Garcia, Gabriela; Radmilovich, Milka et al. (2012) Spatial domains of progenitor-like cells and functional complexity of a stem cell niche in the neonatal rat spinal cord. Stem Cells 30:2020-31 |
| Reali, Cecilia; Fernandez, Anabel; Radmilovich, Milka et al. (2011) GABAergic signalling in a neurogenic niche of the turtle spinal cord. J Physiol 589:5633-47 |
| Rehermann, Maria Ines; Santinaque, Federico Fernando; Lopez-Carro, Beatriz et al. (2011) Cell proliferation and cytoarchitectural remodeling during spinal cord reconnection in the fresh-water turtle Trachemys dorbignyi. Cell Tissue Res 344:415-33 |
| Marichal, Nicolás; García, Gabriela; Radmilovich, Milka et al. (2009) Enigmatic central canal contacting cells: immature neurons in ""standby mode""? J Neurosci 29:10010-24 |
| Rehermann, María Inés; Marichal, Nicolás; Russo, Raúl E et al. (2009) Neural reconnection in the transected spinal cord of the freshwater turtle Trachemys dorbignyi. J Comp Neurol 515:197-214 |
| Russo, Raul E; Reali, Cecilia; Radmilovich, Milka et al. (2008) Connexin 43 delimits functional domains of neurogenic precursors in the spinal cord. J Neurosci 28:3298-309 |
| Trujillo-Cenoz, Omar; Fernandez, Anabel; Radmilovich, Milka et al. (2007) Cytological organization of the central gelatinosa in the turtle spinal cord. J Comp Neurol 502:291-308 |
