ABSTRACT
<p><b>BACKGROUND</b>Sleep/wake disturbances in patients with amyotrophic lateral sclerosis (ALS) are well-documented, however, no animal or mechanistic studies on these disturbances exist. Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation, and may play an important role in sleep disturbances in ALS. In this study, we used SOD1-G93A transgenic mice as an ALS mouse model to investigate the sleep/wake disturbances and their possible mechanisms in ALS.</p><p><b>METHODS</b>Electroencephalogram/electromyogram recordings were performed in SOD1-G93A transgenic mice and their littermate control mice at the ages of 90 and 120 days, and the samples obtained from these groups were subjected to quantitative reverse transcriptase-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>For the first time in SOD1-G93A transgenic mice, we observed significantly increased wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin A and B) at both 90 and 120 days. Correlation analysis confirmed moderate to high correlations between sleep/wake time (total sleep time, wakefulness time, rapid eye movement [REM] sleep time, non-REM sleep time, and deep sleep time) and increase in orexins (prepro-orexin, orexin A and B).</p><p><b>CONCLUSION</b>Sleep/wake disturbances occur before disease onset in this ALS mouse model. Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS. Further studies are required to elucidate the underlying mechanisms in the future.</p>
Subject(s)
Animals , Female , Male , Mice , Amyotrophic Lateral Sclerosis , Genetics , Metabolism , Intracellular Signaling Peptides and Proteins , Genetics , Metabolism , Mice, Transgenic , Neuropeptides , Genetics , Metabolism , Orexins , Reverse Transcriptase Polymerase Chain Reaction , Sleep , Physiology , Superoxide Dismutase , Genetics , Metabolism , Superoxide Dismutase-1 , Wakefulness , PhysiologyABSTRACT
The aim of this present study is to evaluate the therapeutic effect of co-transplantation of neuregulin-1-transfected Schwann cells (SCs) and bone marrow stromal cells (BMSCs) on a rat model of spinal cord hemi-section injuries (Brown-Séquard syndrome), which is relevant to human clinical spinal cord injury. Both in vivo and in vitro data we received demonstrated that co-transplantation BMSCs with NRG1-transfected SCs reduced the size of cystic cavities, promoted axonal regeneration and hind limb functional recovery in comparison with SCs or BMSCs transplantation alone or together, and this treatment could provide important insights into potential therapies of spinal cord hemi-section injuries.
