Acclimatization to middle altitude hypoxia protects against developmental and cognitive deficits caused by acute fetal hypoxia in mice
- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 2
- DOI:
- 10.13294/j.aps.2017.0012
- Key Word:
- 低氧环境适应;神经保护作用;急性胚胎期低氧;发育障碍;认知障碍;hypoxia acclimatization;neuroprotective function;acute fetal hypoxia;developmental disorder;cognitive disorder
Abstract： Acute fetal hypoxia (AFH) can elicit postnatal motor deficits and cognitive impairments.To test whether lifelong acclimatization to middle altitude (MA) hypoxia has protective effects on the impairments caused by AFH,ICR mice bred at 1 900 m altitude for 6-7 generations were evaluated under AFH.On gestation day 9 (GD 9),13 (GD 13) or 17 (GD 17),pregnant mice received a single exposure to acute hypoxia (7％ O2,6 h).Physiological and neurodevelopmental behaviors,motor function (open field),spatial learning and memory (Morris water maze),and anxiety level (elevated plus maze) were examined in the offspring from neonate to adulthood.In the neonatal age,among all the physiological and behavioral landmarks,almost no differences were found in the hypoxia groups.In the juvenile period,no obvious impairments of motor function and anxiety level were found in the hypoxia groups.In the adult period,no obvious impairment of motor function was found in hypoxia groups;Interestingly,AFH groups' offspring showed normal or enhanced long-term spatial memory ability after AFH.These data suggest that AFH cause little abnormalities in the offspring of MA-adapted mice.To further investigate the underlying mechanisms,the neuronal numbers in behavior-related brain areas (accumbens nucleus,basal amygdala and hippocampus) were counted,and the physiological parameters of the blood were measured.The morphological data showed that no obvious neuronal necrosis was found in all hypoxia groups.In addition,blood tests showed that red blood corpuscle count,hemoglobin concentration and hematocrit levels in mice raised at MA were markedly higher in both males and females,compared with controls raised at the sea level.These data suggest that lifelong acclimatization to MA hypoxia has protective effects against development delay,motor deficits and spatial learning and memory impairments induced by AFH,and the protective effects may be due to higher hemoglobin concentration and hematocrit levels in the blood.The findings may provide a better understanding of fetal hypoxia and potential intervention treatments.
- [1]赵彤,于顺,丁爱石,等.低氧预适应增强大鼠海马神经元的耐缺氧能力[J].2001,(1).
- [2]E, Krampl,C, Lees,J M, Bland,etc.Fetal biometry at 4300 m compared to sea level in Peru.[J].2000,16.
- [3]Pichiule P,Chavez JC,LaManna JC.Structural and functional adaptation to hypoxia in the rat brain[J].2004,207(Pt.18).
- [4]Julian,C.G.,Wilson,M.J.,Moore,L.G..Evolutionary adaptation to high altitude: A view from in utero[J].2009,21(5).
- [5]van Patot MC,Valdez M,Becky V.Impact of pregnancy at high altitude on placental morphology in non-native women with and without preeclampsia.[J].2009,30(6).
- [6]Du JZ,Chen QM,Zhang JX,etc.Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8-arm radial maze tasks.[J].2005,65(1).
- [7]Schmutzhard J,Bitsche M,Glueckert R.The cochlea in fetuses with neural tube defects.[J].2009,27(7).
- [8]Steel KP. Brown SDM.,Murdoch JN.,Spurr N.,etc.Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse[J].2003,12(13).
- [9]Fernanda Klein Marcondes,Katia Jacqueline Miguel,Liana Lins Melo,etc.Estrous cycle influences the response of female rats in the elevated plus-maze test[J].2001,74(4-5).
- [10]I A, Zhuravin,N M, Dubrovskaya,N L, Tumanova.Postnatal physiological development of rats after acute prenatal hypoxia.[J].2004,34(8).
- [11]Hava, Golan,Mahmoud, Huleihel.The effect of prenatal hypoxia on brain development: short- and long-term consequences demonstrated in rodent models.[J].2006,9(4).
- [12]Papadopoulou Z,Spandou E,Soubasi V,etc.Erythropoietin prevents long-term sensorimotor deficits and brain injury following neonatal hypoxia-ischemia in rats.[J].2005,1045(1).
- [13]Chiba S,Nishihara M,Kayasuga Y,etc.Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene.[J].2007,185(2).
- [14]Mortola JP,Frappell PB,Aguero L,etc.Birth weight and altitude: a study in Peruvian communities.[J].2000,136(3).
- [15]Dean,J.,Riddle,A.,Hohimer,A.R.,etc.The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant[J].2012,9(2).
- [16]I. A. Zhuravin,N. M. Dubrovskaya.Ontogenetic Characteristics of Behavior in Rats Subjected to Hypoxia on Day 14 or Day 18 of Embryogenesis[J].2010,40(2).
- [17]Millan MJ.The neurobiology and control of anxious states.[J].2003,70(2).
- [18]Harding R,Rees S,Walker D.The biological basis of injury and neuroprotection in the fetal and neonatal brain.[J].2011,29(6).
- [19]Golan H,Hallak M,Sorokin Y,etc.Maternal hypoxia during pregnancy induces fetal neurodevelopmental brain damage: Partial protection by magnesium sulfate.[J].2004,78(3).
- [20]Lu XJ,Weng J,Chen XQ.Hippocampal spine-associated Rap-specific GTPase-activating protein induces enhancement of learning and memory in postnatally hypoxia-exposed mice.[J].2009,162(2).
- [21]Debbie A,Lawlor.Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: findings from the Aberdeen Children of the 1950s prospective cohort study.[J].2005,112.
- [22]D A, Lawlor,S, Ebrahim,G, Davey Smith.Association of birth weight with adult lung function: findings from the British Women's Heart and Health Study and a meta-analysis.[J].2005,60(10).
- [23]Noon K,Ward NL,Keenan E,etc.Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains.[J].2007,102(5).
- [24]Vootele Võikar,Sulev Kõks,Eero Vasar,etc.Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies[J].2001,72(1-2).
- [25]D S, Vasil'ev,N L, Tumanova,I A, Zhuravin.[Change of the neocortex nervous tissue in rat ontogenesis after hypoxia at various terms of embryogenesis].[J].1900,44(3).
- [26]Irene E, Zohn,Anjali A, Sarkar.Modeling neural tube defects in the mouse.[J].2008,84.
- [27]Kumral A,Uysal N,Tugyan K,etc.Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats.[J].2004,153(1).
- [28]LORNA G. MOORE.Fetal Growth Restriction and Maternal Oxygen Transport during High Altitude Pregnancy[J].2003,4(2).
- [29]Kashtutsky I,Hallak M,Sorokin Y,etc.Maternal hypoxia during pregnancy delays the development of motor reflexes in newborn mice.[J].2004,26(1).
- [30]Philip N. Ainslie,Shigehiko Ogoh.Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balance[J].2010,95(2).
- [31]H E, Jones,R L, Balster.Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene.[J].1900,19(4).