Several neurological diseases are associated with or are the cause of movement impairments; among them spinal muscular atrophy (SMA), spinal cord injury, mulZple sclerosis and others are examples with analogous effects on anZ-gravity muscles. Since life support increases people affected survival expectaZons these paZents are likely to be exposed to the effects of the prolonged motor deprivaZon. That can influence not only the motor or metabolic systems but also the nervous system, altering neurogenesis and the interacZon between motoneurons and muscle cells. There is relaZvely li^le informaZon available about the effect of prolonged muscle disuse on neurogenesis; most previous studies describe in vivo changes with small focus on the differenZaZon process or in vitro analysis. Results 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 hind limb unloading model (HU) [1]. Four month old mice were suspended from the tail, HU group, for 14 days, whereas the controls (CTR) were leb 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 SVZ of HU mice show a lower proliferaZon capability compared to CTR (unrestrained) mice with a doubling Zme that is almost 4 Zmes that observed in the CTR. These results are in accord 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 cell cycle are altered compared to the CTR. In addiZon, in NSCs obtained HU animals, the differenZaZon is altered, with a significant reducZon of the number of β-Tubulin III posiZve cells and a co-expression of Glial Fibrillary Acidic Protein, that suggests an incomplete differenZaZon/maturaZon of the NSCs which, most likely, do not reach mature neuronal electrical membrane properZes. NSCs obtained from HU mice have a lower metabolic acZvity with respect to the CTR NSCs as measured by a MTT assay and lactate producZon. Conclusions Motor-deprivaZon is a very frequent condiZon occurring in numerous neurological diseases. A be^er understanding of the effects of motor deprivaZon on neurogenesis, appears relevant as it can open new avenues to design effecZve and appropriate treatments coupled with rehabilitaZon/training intervenZons [3]. The results of this research will certainly contribute to the clarificaZon how situaZons such as the absence of the load and the lack of movement that occurs in people with some neurological diseases may affect the properZes of NSCs and contribute to the negaZve manifestaZons of these condiZons. This research will also help to confirm the role of exercise as a useful treatment for many neurological and neurodegeneraZve diseases.

Motor deprivation in healthy animal models a Galilean approach for movement limiting neurological diseases / D. Bottai, R. Adami, D. Recchia, J. Pagano, M. Colombo, N. Platonova, R. Chiaramonte, R. Bottinelli, M. Canepari. ((Intervento presentato al 21. convegno Cure SMA Researcher Meeting Orlando tenutosi a Orland nel 2017.

Motor deprivation in healthy animal models a Galilean approach for movement limiting neurological diseases

D. Bottai
Primo
;
R. Adami;M. Colombo;N. Platonova;R. Chiaramonte;
2017-07-29

Abstract

Several neurological diseases are associated with or are the cause of movement impairments; among them spinal muscular atrophy (SMA), spinal cord injury, mulZple sclerosis and others are examples with analogous effects on anZ-gravity muscles. Since life support increases people affected survival expectaZons these paZents are likely to be exposed to the effects of the prolonged motor deprivaZon. That can influence not only the motor or metabolic systems but also the nervous system, altering neurogenesis and the interacZon between motoneurons and muscle cells. There is relaZvely li^le informaZon available about the effect of prolonged muscle disuse on neurogenesis; most previous studies describe in vivo changes with small focus on the differenZaZon process or in vitro analysis. Results 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 hind limb unloading model (HU) [1]. Four month old mice were suspended from the tail, HU group, for 14 days, whereas the controls (CTR) were leb 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 SVZ of HU mice show a lower proliferaZon capability compared to CTR (unrestrained) mice with a doubling Zme that is almost 4 Zmes that observed in the CTR. These results are in accord 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 cell cycle are altered compared to the CTR. In addiZon, in NSCs obtained HU animals, the differenZaZon is altered, with a significant reducZon of the number of β-Tubulin III posiZve cells and a co-expression of Glial Fibrillary Acidic Protein, that suggests an incomplete differenZaZon/maturaZon of the NSCs which, most likely, do not reach mature neuronal electrical membrane properZes. NSCs obtained from HU mice have a lower metabolic acZvity with respect to the CTR NSCs as measured by a MTT assay and lactate producZon. Conclusions Motor-deprivaZon is a very frequent condiZon occurring in numerous neurological diseases. A be^er understanding of the effects of motor deprivaZon on neurogenesis, appears relevant as it can open new avenues to design effecZve and appropriate treatments coupled with rehabilitaZon/training intervenZons [3]. The results of this research will certainly contribute to the clarificaZon how situaZons such as the absence of the load and the lack of movement that occurs in people with some neurological diseases may affect the properZes of NSCs and contribute to the negaZve manifestaZons of these condiZons. This research will also help to confirm the role of exercise as a useful treatment for many neurological and neurodegeneraZve diseases.
Settore BIO/13 - Biologia Applicata
Settore BIO/14 - Farmacologia
Settore BIO/09 - Fisiologia
Settore BIO/10 - Biochimica
Motor deprivation in healthy animal models a Galilean approach for movement limiting neurological diseases / D. Bottai, R. Adami, D. Recchia, J. Pagano, M. Colombo, N. Platonova, R. Chiaramonte, R. Bottinelli, M. Canepari. ((Intervento presentato al 21. convegno Cure SMA Researcher Meeting Orlando tenutosi a Orland nel 2017.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/596452
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