Mesenchymal stem cells have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Of these, cerebellar ataxia is a group of disorders characterized by the degeneration of the cerebellum, particularly the Purkinje cells, responsible for motor coordination and control of the motor functions. To analyze the possibility of using bone marrow-derived mesenchymal stem cells in treating ataxia, we transplanted these cells in the cerebellum of newborn Lurcher mutant mice, a very aggressive mouse model characterized by the selective early post-natal death of Purkinje cells in the cerebellum. Two months after the surgical procedure, the treated mice presented significant improvements in the motor behavior tests performed. Histological analysis of the cerebellum indicated that the donor cells had migrated throughout the cerebellum, as well as a significant increase in the number of Purkinje cells. Many grafted stem cells were located adjacent to the Purkinje cell layer, and expressed BDNF, NT-3 or GDNF, neurotrophic factors implicated in Purkinje cell survival. Also, a small percentage of the grafted stem cells had fused with Purkinje cells. Thus, we have shown that mesenchymal stem cells are capable of integrating into the central nervous system, migrate towards the areas where neurodegenerative processes are occurring, and rescue the degenerating cells through cell trophic effects. This is an adequate and feasible model that could be translated into a therapeutic approach for clinical assays in neurodegenerative diseases.
DEA, Additive models, Efficiency measures, Returns to scale, Bounded additive models, C51, C61,
Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain's white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft.
Bariatric surgery (BS) is considered the most effective treatment for morbid obesity. Preoperative body weight is directly associated with a higher surgical morbimortality and physical activity could be effective in the preparation of patients. The aim of this study is to determine the effects of a six-month exercise training program (ETP), combining high-intensity interval training (HIIT) and resistance training in patients awaiting BS. Six candidates awaiting BS (38.78 ± 1.18 kg·m−2; 38.17 ± 12.06 years) were distributed into two groups: the ETP group (experimental group (EG), n = 3) and a control group (CG, n = 3). Anthropometrical and blood pressure (BP), cardiorespiratory fitness and maximal strength were registered before and after the ETP. The EG participated in 93.25% of the sessions, showing reductions in body mass index (BMI) compared to the CG (34.61 ± 1.56 vs. 39.75 ± 0.65, p = 0.006, ANOVA). The inferential analysis showed larger effects on BMI, excess body weight percentage and fat mass, in addition to small to moderate effects in BP and the anthropometric measurements. Peak oxygen uptake normalized to fat-free mass showed likely positive effects with a probability of >95–99%. A six-month ETP seems to be a positive tool to improve body composition, cardiometabolic health, and fitness level in patients awaiting BS, but a larger sample size is needed to confirm these findings.
Aging is associated with sarcopenia. The loss of strength results in decreased muscle mass and motor function. This process accelerates the progressive muscle deterioration observed in older adults, favoring the presence of debilitating pathologies. In addition, sarcopenia leads to a decrease in quality of life, significantly affecting self-sufficiency. Altogether, these results in an increase in economic resources from the National Health Systems devoted to mitigating this problem in the elderly, particularly in developed countries. Different etiological determinants are involved in the progression of the disease, including: neurological factors, endocrine alterations, as well as nutritional and lifestyle changes related to the adoption of more sedentary habits. Molecular and cellular mechanisms have not been clearly characterized, resulting in the absence of an effective treatment for sarcopenia. Nevertheless, physical activity seems to be the sole strategy to delay sarcopenia and its symptoms. The present review intends to bring together the data explaining how physical activity modulates at a molecular and cellular level all factors that predispose or favor the progression of this deteriorating pathology.
Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis.
Adolescence is an important stage for brain maturation. There are many studies of exercise-cognition relations, but there is still a lack of knowledge about the impact of combining different intensities of exercise on adolescents’ cognitive responses. The main objective of this study was to analyze the effect of three physical education sessions (based on Zumba dance) of different intensities (no exercise, predominantly light intensity, and predominantly vigorous intensity) on the inhibition response (measured with the Stroop test) in adolescents. Forty-four adolescent students (age 16.39 ± 0.68) completed a Stroop test before and after the three different physical education sessions. The results show than the predominantly vigorous session represented the strongest stimulus to increase cognitive inhibitory control. This means that the cognitive effect of exercise can be conditioned by exercise intensity and implies the need to control exercise intensity in physical educational programs for adolescents.
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