Transcriptional signature of accessory cells in the lateral line, using the Tnk1bp1:EGFP transgenic zebrafish line

<p>Abstract</p> <p>Background</p> <p>Because of the structural and molecular similarities between the two systems, the lateral line, a fish and amphibian specific sensory organ, has been widely used in zebrafish as a model to study the development/biology of neuroepithelia of the inner ear. Both organs have hair cells, which are the mechanoreceptor cells, and supporting cells providing other functions to the epithelium. In most vertebrates (excluding mammals), supporting cells comprise a pool of progenitors that replace damaged or dead hair cells. However, the lack of regenerative capacity in mammals is the single leading cause for acquired hearing disorders in humans.</p> <p>Results</p> <p>In an effort to understand the regenerative process of hair cells in fish, we characterized and cloned an <it>egfp </it>transgenic stable fish line that trapped <it>tnks1bp1</it>, a highly conserved gene that has been implicated in the maintenance of telomeres' length. We then used this Tg(<it>tnks1bp1</it>:EGFP) line in a FACsorting strategy combined with microarrays to identify new molecular markers for supporting cells.</p> <p>Conclusions</p> <p>We present a Tg(<it>tnks1bp1</it>:EGFP) stable transgenic line, which we used to establish a transcriptional profile of supporting cells in the zebrafish lateral line. Therefore we are providing a new set of markers specific for supporting cells as well as candidates for functional analysis of this important cell type. This will prove to be a valuable tool for the study of regeneration in the lateral line of zebrafish in particular and for regeneration of neuroepithelia in general.</p

NeuroBoricuas: a novel approach for incorporating neuroscience education in schools of Puerto Rico

[EN] Puerto Rico is in dire need of transforming its education system to counter the current economic recession and ensure a future with talented Puerto Ricans at the forefront of scientific research and technology development.  Here we present a group of neuroscientists and educators, the NeuroBoricuas, committed to revolutionize the scientific culture of Puerto Rico by incorporating neuroscience research training and inquiry-based activities in public and private schools. We carry out our vision through diverse methods, such as community outreach activities, where we promote neuroscience literacy using diverse learning activities. In parallel, we are designing a neuroscience course and textbook with educators to be implemented in schools. We also established neuroscience laboratories in K-12 schools and trained science teachers to manage such laboratories, using equipment from the company “Backyard Brains”. These laboratory experiences are integrated into the academic curriculum in high schools and the equipment is also available for students interested in designing their independent research projects. Lastly, we are expanding a network of committed scientists who partner with educators to help nurture future neuroscientists early in their academic endeavors. Here, we describe our trajectory and our approach to transform scientific education in Puerto Rico.We thank Dr. Gregory J. Quirk, Dr. Daniel Colon-Ramos and Dr. Mark Miller for their support. We thank Tim Marzullo, from Backyard Brains, for supporting NeuroBoricuas. We also thank Palabreria, Digi-Serv and Puerto Rico 4.0 for their constant support. We thank all the NeuroBoricuas that selflessly work hard for a better Puerto Rico. This work has been supported by generous donations from the Puerto Rican people, a grant from the University of Puerto Rico Medical Sciences Campus’ Chancellor’s office, and the Grass Foundation.http://ocs.editorial.upv.es/index.php/HEAD/HEAD18Bravo-Rivera, C.; Díaz-Ríos, M.; Aldarondo-Hernández, A.; Santos-Vera, B.; Ramos-Medina, L.; De Jesús-Burgos, M.; Bravo-Rivera, H.... (2018). NeuroBoricuas: a novel approach for incorporating neuroscience education in schools of Puerto Rico. Editorial Universitat Politècnica de València. 1447-1455. https://doi.org/10.4995/HEAD18.2018.8223OCS1447145

Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

Spinal cord injury (SCI) is a devastating condition that produces significant changes in the lifestyle of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI: an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents (tamoxifen and a Src kinase family inhibitor known as PP2) that have been shown in our laboratory to produce neuroprotective (increase cell survival) and/or regenerative (axonal outgrowth) actions. The animal model used in our laboratory is adult female rat (~250 g) with a moderate contusion (12.5 mm) to the spinal cord at the T 10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet (Innovative Research of America, Sarasota, FL, USA) or by intraperitoneal injections (1.5 mg/kg, every 3 days), respectively, to produce a long-term effect (28 days). Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regenerative activity in vertebrates with SCI

Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects