亚磁环境下小鼠生理及运动能力的适应性变化与天人相应理论

目的:探索不同亚磁环境下小鼠生理及运动能力的变化规律,阐释天人相应理论的生物学基础,为未来载人航天生命保障中必须考虑的亚磁效应风险评估提供基础研究依据。方法:8周龄成年雄性C57BL/6小鼠60只,适应性饲养7天后,按照体质量随机分为亥姆霍兹亚磁组、亥姆霍兹对照组、坡莫合金亚磁组、坡莫合金对照组。采用有光照补偿式亥姆霍兹线圈系统(HCS)和无光照屏蔽式坡莫合金亚磁系统(PHS)构建的不同亚磁环境以及相应的地磁场环境进行小鼠长期连续培养,在1个月、3个月、12个月、24个月时,通过热板仪、跑步机、转棒等方法分别检测小鼠热痛觉敏感性,运动能力及身体协调能力的变化。结果:经过3个月亚磁场处理后,坡莫合金亚磁组的热痛觉敏感性明显高于亥姆霍兹对照组、坡莫合金对照组(P<0.01,P<0.05);亥姆霍兹亚磁组运动能力及身体协调能力明显低于其对照组(P<0.05),且坡莫合金对照组运动能力及身体协调能力明显小于亥姆霍兹对照组(P<0.05,P<0.01);处理时间12个月时,2种亚磁处理组在热痛觉敏感度上均高于其对照组(P<0.0001,P<0.01),且坡莫合金对照组小鼠的热痛觉敏感程度要显著高于亥姆霍兹对照组(P<0.05);2种亚磁处理组运动能力及身体协调能力均明显低于其对照组(P<0.05,P<0.01),坡莫合金亚磁组运动能力及身体协调能力明显低于亥姆霍兹亚磁组(P<0.001,P<0.05),坡莫合金对照组运动能力及身体协调能力明显低于亥姆霍兹对照组(P<0.001,P<0.01);24个月时,亚磁组小鼠各指标的差异下降,亥姆霍兹亚磁组和坡莫合金亚磁组饮水量明显高于其对照组(P<0.05,P<0.01),饮食量有上升趋势,坡莫合金亚磁组小鼠的空腹血糖水平较其他3组均明显下降(P<0.05,P<0.01,P<0.001),体质量差异无统计学意义。1个月亚磁处理小鼠各指标暂无差异。结论:长期亚磁场曝露会导致小鼠热痛觉敏感度升高,运动能力及身体协调能力下降,且具有时间累积效应。光照调节可能是挽回亚磁效应的干预途径。

中国空间生命科学40年回顾与展望

我国空间生命科学的探索起源于20世纪60年代,1981年随着空间生命专业委员会的正式成立,依托此专业的学术交流平台,空间生命科学进入多学科并进多机构建设的新阶段.随着中国载人航天及空间探索研究的深入发展,以分支学科或重大问题为牵引,我国在空间生命科学的几个重要领域取得了一系列关键成果.本文从发展历程、研究成果、平台模型、重大项目与后续展望等方面综述了我国空间生命科学40年的发展历程与标志性成果,为后续发展提供借鉴与参考.

The herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a neuroblastoma cells

The herbal medicine Tong Luo Jiu Nao(TLJN)contains geniposide(GP)and ginsenoside Rg1 at a molar ratio of 10:1.Rg1 is the major component of another herbal medicine,panax notoginseng saponin(PNS).TLJN has been shown to strengthen brain function in humans,and in animals it improves learning and memory.We have previously shown that TLJN reduces amyloidogenic processing in Alzheimer’s disease(AD)mouse models.Together this suggests TLJN may be a potential treatment for patients with dementia.Because chronic damage of the central nervous system by formaldehyde(FA)has been presented as a risk factor for age-associated cognitive dysfunction,in the present study we investigated the protective effect of both TLJN and GP in neuron-like cells exposed to FA.FA-exposed murine N2a neuroblastoma cells were incubated with TLJN,its main ingredient GP,as well as PNS,to measure cell viability and morphology,the rate of apoptosis and expression of genes encoding Akt,FOXO3,Bcl2 and p53.The CCK-8 assay,cytoskeletal staining and flow cytometry were used to test cell viability,morphology and apoptosis,respectively.Fluorescent quantitative real-time PCR(qRT-PCR)was used to monitor changes in gene expression,and HPLC to determine the rate of FA clearance.Treatment of N2a cells with 0.09 mmol L?1 FA for 24 h significantly reduced cell viability,changed cell morphology and promoted apoptosis.Both TLJN and GP conferred neuroprotection to FA-treated N2a cells,whereas PNS,which had to be used at lower concentrations because of its toxicity,did not.Our data demonstrate that TLJN can rescue neuronal damage caused by FA and that its main ingredient,GP,has a major role in this efficacy.This presents purified GP as a drug or lead compound for the treatment of AD.

Visualizing the microtubule-associated protein tau in the nucleus

Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial as is evident from transgenic mouse studies.When human tau is over-expressed,it can be immunohistochemically localized to axons and the somatodendritic domain,modeling what is found in neurodegenerative diseases such as Alzheimer’s disease.Yet,in wild-type mice,despite its abundance,tau is difficult to visualize even in the axon.It is even more challenging to detect this protein in the nucleus,where tau has been proposed to protect DNA from damage.To establish a framework for future studies into tau’s nuclear functions,we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain.While depending on the fixation and permeabilization protocol,we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells,we failed to do so in N2a murine neuroblastoma cells.As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form.When either full-length or truncated human tau was expressed,both accumulated in the cytoplasm,but were also found in the nuclear fraction.Because subcellular fractionation methods have their limitations,we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination.Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form.

Transcriptome profile of human neuroblastoma cells in the hypomagnetic field

Research has shown that the hypomagnetic field(HMF)can affect embryo development,cell proliferation,learning and memory,and in vitro tubulin assembly.In the present study,we aimed to elucidate the molecular mechanism by which the HMF exerts its effect,by comparing the transcriptome profiles of human neuroblastoma cells exposed to either the HMF or the geomagnetic field.A total of 2464 differentially expressed genes(DEGs)were identified,216 of which were up-regulated and2248 of which were down-regulated after exposure to the HMF.These DEGs were found to be significantly clustered into several key processes,namely macromolecule localization,protein transport,RNA processing,and brain function.Seventeen DEGs were verified by real-time quantitative PCR,and the expression levels of nine of these DEGs were measured every 6 h.Most notably,MAPK1 and CRY2,showed significant up-and down-regulation,respectively,during the first 6 h of HMF exposure,which suggests involvement of the MAPK pathway and cryptochrome in the early bio-HMF response.Our results provide insights into the molecular mechanisms underlying the observed biological effects of the HMF.

Introduction to the thematic issue “From brain function to therapy”

This thematic issue of Science China Life Sciences,'From brain function to therapy',highlights some of the exciting research being undertaken in the Joint Laboratory of Neuroscience and Cognition,an international scientific collaboration between the Queensland Brain Institute(QBI)at

The role of the N-methyl-D-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells

New neurons are continuously generated from resident pools of neural stem and precursor cells(NSPCs)in the adult brain.There are multiple pathways through which adult neurogenesis is regulated,and here we review the role of the N-methyl-D-aspartate receptor(NMDAR)in regulating the proliferation of NSPCs in the adult hippocampus.Hippocampal-dependent learning tasks,enriched environments,running,and activity-dependent synaptic plasticity,all potently up-regulate hippocampal NSPC proliferation.We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity,and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons.We address how specific NMDAR agonists and antagonists modulate proliferation,both in vivo and in vitro,and then review the evidence supporting the hypothesis that NMDARs are present on NSPCs.We believe it is important to understand the mechanisms underlying the activation of adult neurogenesis,given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons.In conditions such as age-related memory decline,neurodegeneration and psychiatric disease,mature neurons are lost or become defective;as such,stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions.

What did the bronze eye-like prism tell us?

In 1986,the Sanxingdui("Three-Star Mound")Relics were discovered in Guanghan City of Sichuan Province in China.Two major sacrificial pits were excavated and thousands of treasures were discovered,including bronze artifacts,jade wares and potteries.These relics have unveiled the history of the ancient Shu Kingdom during the era of the

Formaldehyde stress

Formaldehyde,one of the most toxic organic compounds,is produced and processed in human cells.The level of human endogenous formaldehyde is maintained at a low concentration(0.01-0.08 mmol L-1 in blood) under physiological conditions,but the concentration increases during ageing(over 65 years old).Clinical trials have shown that urine formaldehyde concentrations are significantly different between elderly Alzheimer's patients(n=91) and normal elderly volunteers(n=38)(P<0.001).Abnormally high levels of intrinsic formaldehyde lead to dysfunction in cognition such as learning decline and memory loss.Excess extracellular and intracellular formaldehyde could induce metabolic response and abnormal modifications of cellular proteins such as hydroxymethylation and hyperphosphorylation,protein misfolding,nuclear translocation and even cell death.This cellular response called formaldehyde stress is dependent upon the concentration of formaldehyde.Chronic impairments of the brain resulted from formaldehyde stress could be one of the mechanisms involved in the process of senile dementia during ageing.

D-ribose,an overlooked player in type 2 diabetes mellitus?

Type 2 diabetes mellitus is a metabolic disorder that is characterized by high blood glucose due to either insulin resistance or insulin deficiency[1].A direct correlation between D-glucose and diabetic complications has long been established,and is the focus of most research in this field.In contrast,D-Ribose has been overlooked so far as a potential risk player in the development of diabetes.

Hypomagnetic field,an ignorable environmental factor in space?

<正>All living organisms on the earth have been exposed to the geomagnetic field(GMF,~50μT),a nature component of the habitability environment,throughout the evolutionary history.However,the environmental magnetic field(MF)in space decreases geometrically with the distance from the ground.The MF magnitude(|B|)at the International Space Station(ISS;near-earth orbit)is similar to the GMF(~80%GMF with limited variation),except that the radial component(Br)exhibits significant variations both in direction and magnitude[1].The environmental MF in outer space is extremely lower than the GMF,called a hypomagnetic field(HMF),e.g.,Martian MF is<5μT,Lunar MF is<300 nT and interplanetary MF is just a few nanotesla[2](Figure 1).Thus,besides micro-gravity(μ-gravity)and cosmic radiation,astronauts have to be exposed and adapt to the HMF condition when onboard in the long-term and long-distance space missions.Even though biological effects of the HMF were

Enzyme with a memory for its substrate?

In the interaction between an enzyme and its substrate,the enzyme is induced by the substrate followed by a change in enzymic conformation to fit the substrate.So far,many laboratories have been studying the neural memory.Recently,