Reduction of movement alters neural stem cells characteristics

Several neurological diseases are associated with or are the cause of movement impairments; among them, spinal cord injury, spinal muscular atrophy, amyotrophic lateral sclerosis and others are examples with analogous effects on anti-gravity muscles. Prolonged motor deprivation can influence not only the motor or metabolic systems but also the nervous system, altering neurogenesis and the interaction between motoneurons and muscle cells. There is relatively little information available about the effect of prolonged muscle disuse on neurogenesis; most previous studies describe in vivo changes with a small focus on the differentiation process or in vitro analysis. In order to remove all the accessory events, we decided to use a Galilean approach where we studied the lack of movement in a healthy wild-type animal using the hindlimb unloading model (HU) [1]. Four-month-old mice were suspended from the tail, HU group, for 14 days, whereas the controls (CTR) were left free to move in a similar cage. At the end of the 14 days, animals were sacrificed, brain dissected and processed for the appropriate experimental procedures [2]. From our in vitro analysis, we determined that Neural Stem Cells (NSCs) derived from the sub ventricular zone of HU mice show a lower proliferation capability compared to CTR (unrestrained) mice with a doubling time that is almost 4 times that observed in the CTR. These results are in accordance with a cytofluorimetric analysis of the cell cycle which indicates that the HU-derived NSCs have a block in G0/G1 together with a shortening of the S and G2/M phases and also some genes involved in the cell cycle are altered compared to the CTR. In addition, in NSCs obtained HU animals, the differentiation is altered, with a significant reduction of the number of β-Tubulin III positive cells and a co-expression of Glial Fibrillary Acidic Protein, that suggests an incomplete differentiation of the NSCs which, most likely, do not reach mature neuronal electrical membrane properties. NSCs obtained from HU mice have a lower metabolic activity with respect to the CTR NSCs as measured by an MTT assay and lactate production [3].Bibliography