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Sciences du comportement

车轮运行环境的复杂性在胎儿酒精中毒综合症的动物模型干预治疗

Published: February 02, 2017
doi:
10.3791/54947
,
1Department of Psychological and Brain Sciences,University of Delaware

Summary

心血管锻炼，并在复杂的环境刺激的经历对啮齿动物大脑内的神经可塑性的多种措施积极效益。本文将讨论这些措施的实施作为“superintervention”相结合的车轮运转和环境的复杂性，将解决这些干预措施的限制。

Abstract

有氧运动（ 例如 ，车轮运行（WR）在动物研究广泛使用）积极的影响neuroplastic潜在的许多措施在大脑中，如成人神经发生，血管生成，以及在啮齿动物中的神经营养因子表达的速率。该干预也被证明以减轻致畸（ 即发育暴露于醇）和与年龄相关的神经变性的在啮齿类动物中产生的负面影响的行为和神经解剖学方面。环境的复杂性（EC）已经显示出产生在皮质和皮质下结构众多neuroplastic好处，可与车轮运行被耦合以增加成人海马增殖和新的细胞的存活。这两个措施的结合提供了一个坚固的“superintervention”（WR-EC），可在一个范围内的神经系统疾病的啮齿动物模型来实现。我们将讨论WR / EC号指令的执行情况及其组成干预措施用作使用产前接触醇在人类的动物模型大鼠的更强大的治疗干预。我们也将讨论的程序元件是绝对必要的干预和哪些可以根据实验者的问题或设施来改变。

Introduction

在不同的环境中饲养早已知道引起神经健康的各种措施的改变。许多研究着眼于在复杂环境下饲养的开始由钻石和罗森茨韦克（ 如开创性研究的有利影响（EC）， 1，2）和格里诺 （ 例如 ，3，4）。统已被证明对在大脑5，6，7突触和细胞变化不可否认的积极影响。 EC可影响大脑区域的多个包括海马8,9和视觉皮层10，11，腹侧纹状体12，13，以及作为脑宽神经免疫功能（在14中综述）。特别兴趣已经从海马的研究开发，当它被证明EC能够通过树突状可塑性9，13增加了齿状回成人出生的颗粒细胞的成活率。最后这一点已经聚集了极大的兴趣，由于文献表明心血管运动促进成年神经的健康受损的脑都15，16，17，18的越来越多。轮运转（WR）是一个容易实现，已被证明是在神经系统疾病或老化17，19，20的啮齿动物模型有利自愿心血管活性的形式。 WR影响生长因子的表达在中央和周围神经系统21，22，23。

（后来）WR和EC组合成一个“superintervention”（WR-EC）（ 即 ，WR其次是30天乳油12天）提供了在海马成年神经稳健增长，并增加了新增殖细胞8的生存之本，在FASD的动物模型不是由单个组件来实现的效果（见下文）。由于WR-EC的两个组成部分大脑13内影响结构的多样化（WR 22审查，欧盟在24综述），该干预的实施可以很容易地应用到神经系统的两个发育和以后的生活发病模型的啮齿动物模型障碍（ 如新生儿酒精暴露，老化，早期生活压力）。

NT“>在青春期和成年早期阶段（ 即出生后30 – 72）WR-EC的整合可以改善一些胎儿酒精谱系障碍的大鼠模型（FASDs）的负面影响8的研究集合。表明，通过在神经解剖学措施9显示显著赤字暴露于来自日龄（PD）的4醇啮齿类如树突复杂25，小脑发育26,27和神经免疫反应28以及受损学习和存储器29，30的表现，31 。这个时间窗口内酒精暴露即使量减少（ 即 PD 7至9）可导致青少年和成年大鼠32学习记忆障碍，同时一些结构再也看不到签名着的神经解剖减值27。许多这些缺陷的-除了在海马依赖性任务的行为障碍-已减轻暴露于这种WR-EC范例8，33或单独WR 25,31。虽然单独WR已广泛使用的介入，WR-EC的组合尚未在文献中，尽管它维持WR 8的相对短期益处能力利用。本文将在青春期讨论WR-EC干预的实施。尽管这种模式是在出生后早期酒精暴露的环境中使用，它可以引入到各种啮齿动物模型来评估脑电位为脑疾病的模型神经可塑性。

Protocol

伦理声明：以下方案经特拉华大学的机构动物护理和使用委员会（IACUC）。 1.发展曝光（或狂欢般的乙醇暴露的模型） 上PD3，确定每只动物的性别和交叉培养任何动物，如果必要保持产仔（8只动物）和性别分布（4-男性：女性4），每个窝内是一致的。 注意：要保持产仔数和性别分布尽可能一致以避免试验的困惑是很重要的。虽然这个协议使用每窝幼仔8（4男4女），另一种垃圾?…

Representative Results

为了评估超级干预的效果，就要看它的每一个构成要素的影响 – WR和EC – 对我们感兴趣的措施。 图1至图 3（下文）出现在利用该范例8先前的出版物。 图4出现在博士论文36。这些数据说明WR-EC对海马成年神经齿状回的影响。所有的图表说明了组手段，具有指示从均值一个标准误差误差线…

Discussion

在上述协议中，我们展示了一个权宜之计的干预抢救新生儿以下酒精暴露神经解剖的赤字。该干预可作为在其他动物模型中的治疗由于每个干预的组分的鲁棒性。在WR的形式自愿心血管活性已经示出受益几个行为结果38,39和诱发脑区功能性塑料的改变如海马（在40中综述）。这部分是由于在啮齿动物的脑实质生长因子和其他神经保护机?…

Divulgations

The authors have nothing to disclose.

Acknowledgements

We would like to dedicate this work to the memory of late Dr. William T. Greenough, a great mentor, a colleague and a friend. This work was supported by NIH/NIAAA grant number AA009838 and NIH/NIGMS COBRE: The Delaware Center for Neuroscience research grant 1P20GM103653 to AYK. We are grateful to the former and current members of Klintsova lab.

Materials

Female Time-pregnant Long Evans Rats Envigo (Formerly: Harlan, Inc.) Average litter size is 8-10 pups
Black India Ink Higgins (Chartpak, Inc.) 44201
Syringes and Injection Needles Becton, Dickinson and Company (BD) Assorted For injection of pawmarking ink, administration of milk-alcohol solution
Ear Punch Kent Scientific Corporation INS750076
Running Wheels Wahmann Labs Wahmann Running Wheel is discontinued. Substitute with  One per cage
EC Cage Martin's Cages, Inc. R-695
Small EC Toys Assorted
Medium EC Toys Assorted Should be able to fit 1-2 rats inside of/ on top of object
Large EC Toys Assorted Should be able to fit 3 or more rats inside of/on top of object
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References

  1. Diamond, M. C., et al. Increases in cortical depth and glia numbers in rats subjected to enriched environment. J Comp Neurol. 128 (1), 117-126 (1966).
  2. Rosenzweig, M. R., Bennett, E. L., Hebert, M., Morimoto, H. Social grouping cannot account for cerebral effects of enriched environments. Brain Res. 153 (3), 563-576 (1978).
  3. Greenough, W. T. Experiential modification of the developing brain. Am Sci. 63 (1), 37-46 (1975).
  4. Volkmar, F. R., Greenough, W. T. Rearing complexity affects branching of dendrites in the visual cortex of the rat. Science. 176 (4042), 1445-1447 (1972).
  5. Greenough, W. T., Volkmar, F. R., Juraska, J. M. Effects of rearing complexity on dendritic branching in frontolateral and temporal cortex of the rat. Exp Neurol. 41 (2), 371-378 (1973).
  6. Sampedro-Piquero, P., Zancada-Menendez, C., Begega, A. Housing condition-related changes involved in reversal learning and its c-Fos associated activity in the prefrontal cortex. Neurosciences. 307, 14-25 (2015).
  7. Sirevaag, A. M., Greenough, W. T. Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, boutons, dendrites, and capillaries. Brain Res. 424 (2), 320-332 (1987).
  8. Hamilton, G. F., Boschen, K. E., Goodlett, C. R., Greenough, W. T., Klintsova, A. Y. Housing in environmental complexity following wheel running augments survival of newly generated hippocampal neurons in a rat model of binge alcohol exposure during the third trimester equivalent. Alcohol Clin Exp Res. 36 (7), 1196-1204 (2012).
  9. Kempermann, G., Kuhn, H. G., Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature. 386 (6624), 493-495 (1997).
  10. Juraska, J. M., Greenough, W. T., Elliott, C., Mack, K. J., Berkowitz, R. Plasticity in adult rat visual cortex: an examination of several cell populations after differential rearing. Behav Neural Biol. 29 (2), 157-167 (1980).
  11. Turner, A. M., Greenough, W. T. Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Res. 329 (1-2), 195-203 (1985).
  12. Brenes, J. C., Rodriguez, O., Fornaguera, J. Differential effect of environment enrichment and social isolation on depressive-like behavior, spontaneous activity and serotonin and norepinephrine concentration in prefrontal cortex and ventral striatum. Pharmacol Biochem Behav. 89 (1), 85-93 (2008).
  13. Kolb, B., Gorny, G., Soderpalm, A. H., Robinson, T. E. Environmental complexity has different effects on the structure of neurons in the prefrontal cortex versus the parietal cortex or nucleus accumbens. Synapse. 48 (3), 149-153 (2003).
  14. Singhal, G., Jaehne, E. J., Corrigan, F., Baune, B. T. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment. Front Cell Neurosci. 8, 97 (2014).
  15. Helfer, J. L., Goodlett, C. R., Greenough, W. T., Klintsova, A. Y. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt. Brain Res. 1294, 1-11 (2009).
  16. van Praag, H., et al. Functional neurogenesis in the adult hippocampus. Nature. 415 (6875), 1030-1034 (2002).
  17. van Praag, H., Shubert, T., Zhao, C., Gage, F. H. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 25 (38), 8680-8685 (2005).
  18. Vivar, C., Peterson, B. D., van Praag, H. Running rewires the neuronal network of adult-born dentate granule cells. Neuroimage. 1 (131), 29-41 (2015).
  19. Mustroph, M. L., et al. Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice. Eur J Neurosci. 41 (2), 216-226 (2015).
  20. Patten, A. R., et al. Long-term exercise is needed to enhance synaptic plasticity in the hippocampus. Learn Mem. 20 (11), 642-647 (2013).
  21. Carro, E., Nunez, A., Busiguina, S., Torres-Aleman, I. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci. 20 (8), 2926-2933 (2000).
  22. Cotman, C. W., Berchtold, N. C. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 25 (6), 295-301 (2002).
  23. Praag, H., Fleshner, M., Schwartz, M. W., Mattson, M. P. Exercise, energy intake, glucose homeostasis, and the brain. J Neurosci. 34 (46), 15139-15149 (2014).
  24. van Praag, H., Kempermann, G., Gage, F. H. Neural consequences of environmental enrichment. Nat Rev Neurosci. 1 (3), 191-198 (2000).
  25. Hamilton, G. F., Criss, K. J., Klintsova, A. Y. Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats. Synapse. 69 (8), 405-415 (2015).
  26. Goodlett, C. R., Thomas, J. D., West, J. R. Long-term deficits in cerebellar growth and rotarod performance of rats following "binge-like" alcohol exposure during the neonatal brain growth spurt. Neurotoxicol Teratol. 13 (1), 69-74 (1991).
  27. Goodlett, C. R., Lundahl, K. R. Temporal determinants of neonatal alcohol-induced cerebellar damage and motor performance deficits. Pharmacol Biochem Behav. 55 (4), 531-540 (1996).
  28. Boschen, K., Ruggiero, M., Klintsova, A. Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus. Neurosciences. 324, 355-366 (2016).
  29. Goodlett, C. R., Peterson, S. D. Sex differences in vulnerability to developmental spatial learning deficits induced by limited binge alcohol exposure in neonatal rats. Neurobiol Learn Mem. 64 (3), 265-275 (1995).
  30. Murawski, N. J., Klintsova, A. Y., Stanton, M. E. Neonatal alcohol exposure and the hippocampus in developing male rats: effects on behaviorally induced CA1 c-Fos expression, CA1 pyramidal cell number, and contextual fear conditioning. Neurosciences. 206, 89-99 (2012).
  31. Thomas, J. D., Sather, T. M., Whinery, L. A. Voluntary exercise influences behavioral development in rats exposed to alcohol during the neonatal brain growth spurt. Behav Neurosci. 122 (6), 1264-1273 (2008).
  32. Hamilton, G. F., et al. Neonatal alcohol exposure disrupts hippocampal neurogenesis and contextual fear conditioning in adult rats. Brain Res. 1412, 88-101 (2011).
  33. Hamilton, G. F., et al. Exercise and environment as an intervention for neonatal alcohol effects on hippocampal adult neurogenesis and learning. Neurosciences. 265, 274-290 (2014).
  34. Kelly, S. J., Lawrence, C. R., Nagy, L. E. . Alcohol: Methods and Protocols. , (2008).
  35. Helfer, J. L., et al. Binge-like postnatal alcohol exposure triggers cortical gliogenesis in adolescent rats. J Comp Neurol. 514 (3), 259-271 (2009).
  36. Hamilton, G. F. . Behavioral Interventions to Alleviate the Impact of Neonatal Alcohol Exposure on Cell Morphology in the Rodent Hippocampus and Medial Prefrontal Cortex. Doctor of Philosophy thesis. , (2012).
  37. Klintsova, A. Y., et al. Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure. Alcohol Clin Exp Res. 31 (12), 2073-2082 (2007).
  38. Brockett, A. T., LaMarca, E. A., Gould, E. Physical exercise enhances cognitive flexibility as well as astrocytic and synaptic markers in the medial prefrontal cortex. PLoS One. 10 (5), e0124859 (2015).
  39. Creer, D. J., Romberg, C., Saksida, L. M., van Praag, H., Bussey, T. J. Running enhances spatial pattern separation in mice. Proc Natl Acad Sci U S A. 107 (5), 2367-2372 (2010).
  40. Patten, A. R., et al. The benefits of exercise on structural and functional plasticity in the rodent hippocampus of different disease models. Brain Plast. 1 (1), 97-127 (2015).
  41. Van der Borght, K., et al. Physical exercise leads to rapid adaptations in hippocampal vasculature: temporal dynamics and relationship to cell proliferation and neurogenesis. Hippocampus. 19 (10), 928-936 (2009).
  42. Johansson, B. B., Belichenko, P. V. Neuronal plasticity and dendritic spines: effect of environmental enrichment on intact and postischemic rat brain. J Cereb Blood Flow Metab. 22 (1), 89-96 (2002).
  43. Sirevaag, A. M., Greenough, W. T. Differential rearing effects on rat visual cortex synapses. II. Synaptic morphometry. Brain Res. 351 (2), 215-226 (1985).
  44. Pham, T. M., Winblad, B., Granholm, A. C., Mohammed, A. H. Environmental influences on brain neurotrophins in rats. Pharmacol Biochem Behav. 73 (1), 167-175 (2002).
  45. Patten, A. R., et al. Long-term exercise is needed to enhance synaptic plasticity in the hippocampus. Learn Mem. 20 (11), 642-647 (2013).
  46. Patten, A. R., et al. The Benefits of Exercise on Structural and Functional Plasticity in the Rodent Hippocampus of Different Disease Models. Brain Plasticity. 1 (1), 97-127 (2015).
  47. Abou-Ismail, U. A. Are the effects of enrichment due to the presence of multiple items or a particular item in the cages of laboratory rat?. Appl Ani Behav Sci. 134 (1-2), 72-82 (2011).
  48. Stranahan, A. M., Khalil, D., Gould, E. Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci. 9 (4), 526-533 (2006).
  49. Boschen, K. E., Hamilton, G. F., Delorme, J. E., Klintsova, A. Y. Activity and social behavior in a complex environment in rats neonatally exposed to alcohol. Alcohol. 48 (6), 533-541 (2014).
  50. Artola, A., et al. Long lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment. Eur J Neurosci. 23 (1), 261-272 (2006).
  51. Bergami, M., et al. A critical period for experience-dependent remodeling of adult-born neuron connectivity. Neuron. 85 (4), 710-717 (2015).
  52. Fréchette, M., Rennie, K., Pappas, B. A. Developmental forebrain cholinergic lesion and environmental enrichment: behaviour, CA1 cytoarchitecture and neurogenesis. Brain Res. 1252, 172-182 (2009).
  53. Rogers, J., et al. Dissociating the therapeutic effects of environmental enrichment and exercise in a mouse model of anxiety with cognitive impairment. Transl Psychiatry. 6, e794 (2016).

Tags

Wheel RunningEnvironmental ComplexityAnimal ModelFASDRehabilitationNeuroplasticityExerciseSocial ExerciseExploratory BehaviorsNeurological DevelopmentAdolescenceHealth MaintenanceAdulthoodVoluntary Cardiovascular ExerciseControlled Laboratory SettingRevolutionsWeightDevelopmental DayGalvanized Steel CagesMultiple LevelsBeddingFood And Water DispensersNovel Colorful ObjectsToysNovelty

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Gursky, Z. H., Klintsova, A. Y. Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD. J. Vis. Exp. (120), e54947, doi:10.3791/54947 (2017).
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