113 research outputs found

    The Mice Drawer System (MDS) Experiment and the Space Endurance Record-Breaking Mice

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    The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28th, 2009. MDS returned to Earth on November 27th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages

    Synergistic association of valproate and resveratrol reduces brain injury in ischemic stroke

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    Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275), respectively, an activator of the AMP-activated kinase (AMPK)-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs), synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker. In cortical neurons previously exposed to oxygen glucose deprivation (OGD), valproate elicited neuroprotection at 100 nmol/mL concentration when used alone and at 1 nmol/mL concentration when associated with resveratrol (3 nmol/mL). Resveratrol and valproate restored the acetylation of histone H3 (K9/18), and they reduced the RelA(K310) acetylation and the Bim level in neurons exposed to OGD. Chromatin immunoprecipitation analysis showed that the synergistic drug association impaired the RelA binding to the Bim promoter, as well as the promoter-specific H3 (K9/18) acetylation. In mice subjected to 60 min of middle cerebral artery occlusion (MCAO), the association of resveratrol 680 µg/kg and valproate 200 µg/kg significantly reduced the infarct volume as well as the neurological deficits. The present study suggests that valproate and resveratrol may represent a promising ready-to-use strategy to treat post-ischemic brain damage

    Drain Brain: monitorare il drenaggio cerebrale negli astronauti per prevenire problemi cardiovascolari

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    Un importante obbiettivo della ricerca spaziale internazionale, in preparazione all'esplorazione umana della Luna e di Marte, è quello di tutelare la salute degli astronauti. Il volo spaziale induce importanti alterazioni a carico di diversi sistemi fisiologici e queste risposte adattative inducono un generale decondizionamento dell'organismo. I programmi di ricerca medica hanno lo scopo di assicurare la salute degli astronauti che affronteranno viaggi spaziali oltre l'orbita bassa, permetterne la pronta operatività una volta arrivati a destinazione e consentirne un sicuro recupero al rientro sulla Terra. Fra i programmi messi in campo dall'Agenzia Spaziale Italiana (ASI), gli esperimenti denominati Drain Brain, svolti in collaborazione con l'Università di Ferrara, sono particolarmente esemplificativi da questo punto di vista. Il progetto, iniziato con la collaborazione di Samantha Cristoforetti nel 2014, ha permesso di dimostrare il funzionamento di un pletismografo per lo studio del circolo cerebrale ed il ritorno venoso dall'encefalo al cuore in condizioni di microgravità. Nei prossimi due anni, grazie al progetto Drain Brain 2.0, gli equipaggi della Stazione Spaziale Internazionale verranno studiati con una nuova versione del sensore pletismografico, sincronizzato con l'elettrocardiogramma, per valutare l'efficienza cardiaca ed il drenaggio cerebrale in rapporto a sintomi come vista offuscata, intorpidimento, annebbiamento o il temuto insorgere di una trombosi giugulare, legata al rallentamento del flusso per assenza del gradiente gravitazionale. Drain Brain 2.0 genererà anche importanti ritorni a Terra, chiudendo il circolo virtuoso dell'applicazione terrestre della ricerca condotta nello Spazio. La nuova strumentazione è di fatto ideale per un uso in telemedicina su pazienti cardiopatici o con problemi cognitivi

    Drain Brain: monitorare il drenaggio cerebrale negli astronauti per prevenire problemi cardiovascolari

    Get PDF
    Un importante obbiettivo della ricerca spaziale internazionale, in preparazione all'esplorazione umana della Luna e di Marte, è quello di tutelare la salute degli astronauti. Il volo spaziale induce importanti alterazioni a carico di diversi sistemi fisiologici e queste risposte adattative inducono un generale decondizionamento dell'organismo. I programmi di ricerca medica hanno lo scopo di assicurare la salute degli astronauti che affronteranno viaggi spaziali oltre l'orbita bassa, permetterne la pronta operatività una volta arrivati a destinazione e consentirne un sicuro recupero al rientro sulla Terra. Fra i programmi messi in campo dall'Agenzia Spaziale Italiana (ASI), gli esperimenti denominati Drain Brain, svolti in collaborazione con l'Università di Ferrara, sono particolarmente esemplificativi da questo punto di vista. Il progetto, iniziato con la collaborazione di Samantha Cristoforetti nel 2014, ha permesso di dimostrare il funzionamento di un pletismografo per lo studio del circolo cerebrale ed il ritorno venoso dall'encefalo al cuore in condizioni di microgravità. Nei prossimi due anni, grazie al progetto Drain Brain 2.0, gli equipaggi della Stazione Spaziale Internazionale verranno studiati con una nuova versione del sensore pletismografico, sincronizzato con l'elettrocardiogramma, per valutare l'efficienza cardiaca ed il drenaggio cerebrale in rapporto a sintomi come vista offuscata, intorpidimento, annebbiamento o il temuto insorgere di una trombosi giugulare, legata al rallentamento del flusso per assenza del gradiente gravitazionale. Drain Brain 2.0 genererà anche importanti ritorni a Terra, chiudendo il circolo virtuoso dell'applicazione terrestre della ricerca condotta nello Spazio. La nuova strumentazione è di fatto ideale per un uso in telemedicina su pazienti cardiopatici o con problemi cognitivi

    Effects of recombinant Irisin on the musculoskeletal system of hind-limb suspended mice

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    We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass, driving positive effects on cortical mineral density and geometry in vivo (1). Here we demonstrated that r-Irisin treatment prevents bone loss in hind-limb suspended mice when administered during suspension and recovers bone mass when mice were injected after a suspension period (4 weeks) during which they developed bone loss. Micro computed tomography of femurs showed that r-Irisin treatment positively affected both cortical and trabecular bone. As expected, unloaded mice treated with vehicle displayed a remarkable decrease of cortical and trabecular bone mineral density (BMD), whereas in Irisin-treated unloaded mice no loss of BMD was observed with respect to control mice kept under normal loading. Likewise, by treating mice after they already developed disuse-induced bone loss, r-Irisin was able to restore the damaged mineral component. Furthermore, trabecular bone volume fraction (BV/TV), which dramatically decreased in unloaded mice, was prevented by r-Irisin therapy. In particular, r-Irisin treatment preserved the number of trabeculae (Tb.N) and the fractal dimension, an index of optimal micro-architectural complexity of trabecular bone.We also showed that r-Irisin treatment protects muscle mass suffering from atrophy during unloading. Thus, unloaded mice treated with vehicle displayed a severe loss of muscle mass, as confirmed by ~ 60% decline of vastus lateralis weight and ~33% decrease of fiber cross-sectional area. Conversely, Irisin-treated unloaded mice showed no loss of muscle weight and similar fiber cross-sectional area to control mice. Our data reveal for the first time that r-Irisin treatment prevents and retrieves disuse-induced bone loss and muscle atrophy. These findings may lead to develop an Irisin-based therapy for the prevention and treatment of osteoporosis and sarcopenia in all patients who cannot perform physical activity, as occurs during aging and immobility, and it could also represent a countermeasure for astronauts exposed to microgravity during space flight missions.This work was supported in part by ERISTO grant (to M.G.), by MIUR grant ex60% (to M.G.) and by SIOMMMS grant (to G.C.)

    Treatment with r-irisin prevents and recovers disuse-induced bone loss and muscle atrophy

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    Irisin is a hormone-like myokine secreted from skeletal muscle in response to exercise. We previously showed that treatment with recombinant Irisin (r-Irisin) in healthy mice improved cortical bone mass and geometry, supporting the idea that Irisin recapitulates some of the most important benefits of physical exercise on the skeleton and plays protective role on bone health (1). Here we show that treatment with r-Irisin prevented bone loss in hind-limb suspended mice when administered during suspension and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks. MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented the dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin inhibited muscle mass decline during unloading, keeping proper fiber cross-sectional area. Notably, the decrease in myosin type II expression (MyHC II) in vastus lateralis of unloaded mice treated with r-Irisin was completely prevented. Our data reveal that r-Irisin treatment protects from disuse induced bone loss and muscle atrophy in mice. If these results will translate to humans, they may support a promising clinical strategy for the prevention and treatment of both osteoporosis and sarcopenia, particularly applicable to those patients who cannot perform physical activity, as occurs during aging, immobility and microgravity during space flight missions

    Irisin injected mice display increased tibial cortical mineral density and polar moment of inertia

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    It has been recently reported that, after physical activity, the skeletal muscle releases Irisin, the newly identified myokine able of driving transition of white adipocytes into brown [1]. This result supported the role of skeletal muscle as endocrine organ, suggesting that it could target other tissues besides adipose tissue. In our previous work, we demonstrated that conditioned media collected from primary myoblasts of exercised mice were able to increase OB differentiation and this effect was Irisinmediated [2]. Here we show that Irisin has positive effect on cortical mineral density and geometry in vivo. Young male mice were injected with r-Irisin and cortical bone adaptation was analyzed by micro-CT at tibial midshaft. Our results show that cortical tissue mineral density is significantly increased in Irisin-injected mice compared to vehicle-injected littermates (+7.15%; p<0.01). Furthermore, this higher density of calcium hydroxyapatite at cortical site is accompanied by increase in periosteal circumference (+7.5%; p<0.03) and polar moment of Inertia (pMOI +19,21%; p<0,01). A greater pMOI indicates stronger resistance of a long bone to torsion and, together with higher bone mineral density, suggests higher protection against fracture. The effect of Irisin is fully comparable to the effect of physical activity that is widely accepted method for increasing bone mineral density and bone size in healthy populations. In view of further proving the involvement of Irisin in bone metabolism, we validate its direct effect on osteoblasts in vitro. Phosphorylation of the MAP kinase ERK and the expression of Atf4 were significantly increased after Irisin treatment, as well as ALP and pro-Collagen I mRNA expression. Our data highlight a novel link in muscle-fat-bone axis demonstrating that Irisin targets bone tissue directly, driving positive effects on cortical mineral density and geometry in vivo. These findings would expand the research of exercise-mimetic drugs that might be widely used to treat osteoporotic patients who are suffering from immobilization and cannot perform physical activity
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