Early Expression of Neuronal Dopaminergic Markers in a Parkinson's Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs).

BACKGROUND: Parkinson's Disease (PD) is a common neurodegenerative disorder affecting the dopaminergic (DAergic) system. Replacement therapy is a promising alternative aimed at reconstructing the cytoarchitecture of affected brain regions in PD. Experimental approaches, such as the replacement of DAergic neurons with cells obtained from the Enteric Nervous System (ENS) has yet to be explored. OBJECTIVE: To establish and characterize a cell replacement strategy with ENS Cells (ENSCs) in a PD model in rats. METHODS: Since ENSCs can develop mature DAergic phenotypes, here we cultured undifferentiated cells from the myenteric plexus of newborn rats, establishing that they exhibit multipotential characteristics. These cells were characterized and further implanted in the Substantia nigra pars compacta (SNpc) of adult rats previously lesioned by a retrograde degenerative model produced by intrastriatal injection of 6-Hydroxydopamine (6-OHDA). DAergic markers were assessed in implants to validate their viability and possible differentiation once implanted. RESULTS: Cell cultures were viable, exhibited stem cell features and remained partially undifferentiated until the time of implant. The retrograde lesion induced by 6-OHDA produced DAergic denervation, reducing the number of fibers and cells in the SNpc. Implantation of ENSCs in the SNpc of 6-OHDAlesioned rats was tracked after 5 and 10 days post-implant. During that time, the implant increased selective neuronal and DAergic markers, Including Microtubule-Associated Protein 2 (MAP-2), Dopamine Transporter (DAT), and Tyrosine Hydroxylase (TH). CONCLUSION: Our novel results suggest that ENSCs possess a differentiating, proliferative and restorative potential that may offer therapeutic modalities to attenuate neurodegenerative events with the inherent demise of DAergic neurons.

A dysfunctional family environment and a high body fat percentage negatively affect telomere length in Mexican boys aged 8-10 years.

AIM: The aim of this study was to determine whether a direct relationship existed between absolute telomere length (aTL), obesity and familial functionality in a group of Mexican children. METHODS: We recruited 134 children (52% boys) aged 8-10 years during regular primary care check-ups in 2016 and evaluated physical activity (PA), feeding practices, anthropometrics, body fat percentage (BF%) and family dysfunction. Optimised quantitative PCR determined aTL from genomic deoxyribonucleic acid isolated from saliva samples. RESULTS: Boys with a healthy BF% showed a higher aTL than their high BF% counterparts (P < .01). aTL was higher in children who performed PA than their sedentary counterparts (P < .05). Alarmingly, 90% of the children belonged to dysfunctional families and a dysfunctional family was correlated with a higher BF% (r = -.57). Negative correlations between the BF% and aTL (r = -.1765) and the BF% and time dedicated to PA (r = -.031) were observed in boys. On the contrary, we found a positive correlation between the aTL and weekly PA (r = .1938). These correlations were not observed in girls. CONCLUSION: Telomere shortening was associated with a high BF% in boys, but not girls. Dysfunctional families were also a key factor. School PA programmes should be mandatory.

Optimizing neurogenic potential of enteric neurospheres for treatment of neurointestinal diseases.

BACKGROUND: Enteric neurospheres derived from postnatal intestine represent a promising avenue for cell replacement therapy to treat Hirschsprung disease and other neurointestinal diseases. We describe a simple method to improve the neuronal yield of spontaneously formed gut-derived neurospheres. MATERIALS AND METHODS: Enteric neurospheres were formed from the small and large intestines of mouse and human subjects. Neurosphere size, neural crest cell content, cell migration, neuronal differentiation, and neuronal proliferation in culture were analyzed. The effect of supplemental neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF) and endothelin-3, was also assessed. RESULTS: Mouse small intestine-derived neurospheres contained significantly more P75-expressing neural crest-derived cells (49.9 ± 15.3% versus 21.6 ± 11.9%, P < 0.05) and gave rise to significantly more Tuj1-expressing neurons than colon-derived neurospheres (69.9 ± 8.6% versus 46.2 ± 15.6%, P < 0.05). A similar pattern was seen in neurospheres isolated from human small and large intestine (32.6 ± 17.5% versus 10.2 ± 8.2% neural crest cells, P < 0.05; 29.7 ± 16.4% versus 16.0 ± 13.5% enteric neurons, P < 0.05). The addition of GDNF to the culture media further improved the neurogenic potential of small intestinal neurospheres (75.9 ± 4.0% versus 67.8 ± 5.8%, P < 0.05) whereas endothelin-3 had no effect. CONCLUSIONS: Enteric neurospheres formed from small intestine and supplemented with GDNF yield an enriched population of neural crest-derived progenitor cells and give rise to a high density of enteric neurons.

Clinical implications of thyroid hormones effects on nervous system development.

Thyroid hormones have an important role throughout prenatal and postnatal nervous system development. They are involved in several processes such as neurogenesis, gliogenesis, myelination, synaptogenesis, etc., as shown in many cases of deficiency like congenital hypothyroidism or hypothyroxinemia. Those pathologies if untreated could lead to severe damages in cognitive, motor, neudoendocrine functions among other effects. Some could be reversed after adequate supplementation of thyroid hormones at birth, however there are other cellular processes highly sensitive to low levels of thyroid hormones and lasting a limited period of time during which if thyroid hormone action is lacking or deficient, the functional and structural damages would produce permanent defects.

T3 differentially regulates TRH expression in developing hypothalamic neurons in vitro.

Triiodothyronine (T3) plays an important role during development of the central nervous system. T3 effects on gene expression are determined in part by the type of thyroid hormone receptors (TRs) expressed in a given cell type. Previous studies have demonstrated that thyrotropin releasing hormone (TRH) transcription in the adult hypothalamus is subjected to negative regulation by thyroid hormones. However, the role of T3 on the development of TRH expression is unknown. In this study we used primary cultures derived from 17-day-old fetal rat hypothalamus to analyze the effects of T3 on TRH gene expression during development. T3 increased TRH mRNA expression in immature cultures, but decreased it in mature cultures. In addition, T3 up-regulated TRalpha1 and TRbeta2 mRNA expression. TRalpha1 expression coincided chronologically with that of TRH in the rat hypothalamus in vivo. Maturation of TRH expression in the hypothalamus may involve T3 acting through TRalpha1.

Lesión de médula espinal y medicina regenerativa: [revisión] / Spinal cord injury and regenerative medicine: [review]

La lesión medular (LM) es un problema que afecta sobre todo a la población en edad laboral y, por lo tanto, sus repercusiones rebasan el ámbito familiar. La LM es irreversible para la mitad de las víctimas y en la actualidad los tratamientos existentes consisten en la asistencia y la estabilización espinal. Con el reconocimiento de la existencia de células madre (CM), el tratamiento de la LM ha recibido otro enfoque. Las CM se encargan de la renovación de los tejidos durante la vida del individuo y su reparación en caso de lesión. Las CM más atractivas desde el punto de vista terapéutico son las capaces de generar diversos tejidos, obtenibles con facilidad, y cuya manipulación es aceptable en términos éticos. En este artículo se presentan algunos de los estudios realizados con CM de diversos orígenes y su aplicación al tratamiento de la LM.

Spinal cord injury (SCI) is a trauma problem striking mainly working age adults, therefore affecting society beyond the victim’s family circle. Most of the victims of SCI will never recover; therapy for this type of injury consists basically on spinal cord support and stabilization. With the discovery of stem cells (SC), SCI treatment has been given another chance. Stem cells are responsible for tissue renewal throughout the individual’s life, as well as tissue repair when needed. From the therapeutic point of view, the most appealing SC are those capable of generating a variety of tissues, those easily harvested, and finally, those ethically unquestioned. This article summarizes some studies carried with SC of various origins and their application to SCI treatment.

[Spinal cord injury and regenerative medicine]. / Lesión de médula espinal y medicina regenerativa.

Spinal cord injury (SCI) is a trauma problem striking mainly working age adults, therefore affecting society beyond the victims family circle. Most of the victims of SCI will never recover; therapy for this type of injury consists basically on spinal cord support and stabilization. With the discovery of stem cells (SC), SCI treatment has been given another chance. Stem cells are responsible for tissue renewal throughout the individuals life, as well as tissue repair when needed. From the therapeutic point of view, the most appealing SC are those capable of generating a variety of tissues, those easily harvested, and finally, those ethically unquestioned. This article summarizes some studies carried with SC of various origins and their application to SCI treatment.

Biology of the adult enteric neural stem cell.

An increasing body of evidence has accumulated in recent years supporting the existence of neural stem cells in the adult gut. There are at least three groups that have obtained them using different methodologies and have described them in vitro. There is a growing amount of knowledge on their biology, but many questions are yet unanswered. Among these questions is whether these cells are part of a permanent undifferentiated pool or are recruited in a regular basis; in addition, the factors and genes involved in their survival, proliferation, migration, and differentiation are largely unknown. Finally, with between 10 and 20% of adults suffering from diseases involving the enteric nervous system, most notably irritable bowel syndrome and gastroesophageal reflux, what is the possible role of enteric nervous stem cells in health and disease?