International Experimental Central Nervous System Injury & Repair (IECNSIR), Dept. of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
Department of Neurology, Bethune International Peace Hospital, Zhongshan Road (West), Shijiazhuang, Hebei Province, P.R. China.
Int Rev Neurobiol. 2023;171:125-162. doi: 10.1016/bs.irn.2023.05.009. Epub 2023 Sep 22.
Sleep deprivation is quite frequent in military during combat, intelligence gathering or peacekeeping operations. Even one night of sleep deprivation leads to accumulation of amyloid beta peptide burden that would lead to precipitation of Alzheimer's disease over the years. Thus, efforts are needed to slow down or neutralize accumulation of amyloid beta peptide (AβP) and associated Alzheimer's disease brain pathology including phosphorylated tau (p-tau) within the brain fluid environment. Sleep deprivation also alters serotonin (5-hydroxytryptamine) metabolism in the brain microenvironment and impair upregulation of several neurotrophic factors. Thus, blockade or neutralization of AβP, p-tau and serotonin in sleep deprivation may attenuate brain pathology. In this investigation this hypothesis is examined using nanodelivery of cerebrolysin- a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies against AβP, p-tau and serotonin (5-hydroxytryptamine, 5-HT). Our observations suggest that sleep deprivation induced pathophysiology is significantly reduced following nanodelivery of cerebrolysin together with monoclonal antibodies to AβP, p-tau and 5-HT, not reported earlier.
在战斗、情报收集或维和行动中，军人经常会遭受睡眠剥夺。即使一晚上的睡眠剥夺也会导致淀粉样β肽（amyloid beta peptide）负担的积累，从而导致多年后阿尔茨海默病的发生。因此，需要努力减缓或中和淀粉样β肽（AβP）的积累以及相关的阿尔茨海默病脑病理学，包括脑内液环境中的磷酸化tau（p-tau）。睡眠剥夺还会改变大脑微环境中的 5-羟色胺（serotonin，5-HT）代谢，并损害几种神经营养因子的上调。因此，在睡眠剥夺时阻断或中和 AβP、p-tau 和 5-HT 可能会减轻脑病理学。在这项研究中，使用脑活素（cerebrolysin）的纳米递送来检验这一假说，脑活素是几种神经营养因子和活性肽片段的平衡组合，同时还有针对 AβP、p-tau 和 5-HT（5-羟色胺）的单克隆抗体。我们的观察表明，与单独使用 AβP、p-tau 和 5-HT 的单克隆抗体相比，脑活素联合单克隆抗体进行纳米递药后，睡眠剥夺引起的病理生理学显著减少，这在以前的研究中并未报道过。
