Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood.
Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood.
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DOI：
10.1016/j.neuroscience.2013.03.058
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发表时间：
2013-08-06
期刊：
影响因子：
3.3
通讯作者：
Crews FT
中科院分区：
文献类型：
--
作者：
Ehlers CL;Liu W;Wills DN;Crews FT
过量饮酒在青少年中很普遍，可能导致持久的神经行为后果。使用动物模型来研究青少年酒精暴露的优点是允许必要的控制，以评估乙醇对大脑的影响，并将这种影响与遗传背景和其他环境损伤分开。在本研究中，适度的乙醇蒸汽暴露的影响，在青春期，对神经发生和行为的措施进行了评估，在两个不同的时间后，乙醇撤退，在成年期。从PD 23-PD 58（平均血液乙醇浓度（BEC）：163 mg%），将两组Wistar大鼠均暴露于间歇性乙醇蒸汽（14小时给药/10小时停药/天）35-36天。在第一组中，在大鼠从蒸汽中撤出后，随后评估其自发活动、在开放场地中的冲突行为和在强迫游泳测试中的行为，然后在72天龄时处死。第二组大鼠从蒸汽中取出并注射溴脱氧尿苷（BrdU）5天。在接下来的8周内，还评估了它们的自发活动、开放场地中的冲突行为和强迫游泳测试中的行为，然后在113/114日龄时处死。对所有大鼠进行灌注，进行组织化学分析。乙醇蒸汽暴露的大鼠表现出活动减退的运动和更少的焦虑样和/或更多的“去抑制”的行为在开放领域的冲突。免疫反应性的定量分析显示，在乙醇蒸汽暴露的大鼠中，在72天时，神经发生、祖细胞增殖的测量（如通过双皮质素（DCX）、Ki 67所指示的）和细胞死亡的标记物增加（如通过裂解的半胱天冬酶-3和Fluoro-Jade所指示的）显著减少，并且在114天时，双皮质素（DCX）减少，裂解的半胱天冬酶-3增加。通过BrdU+评估，暴露于蒸汽的动物在114天处死时祖细胞存活率降低。在DCX标记的细胞计数中观察到的减少与停药后24小时的活动减退显著相关，以及在终止蒸汽暴露后2周和8周的旷场冲突试验中较少的焦虑样和/或更多的“去抑制”行为。这些研究表明，与神经发生减少相关的去抑制行为的行为测量均受到Wistar大鼠青春期酒精暴露和戒断的显著和持续影响。
Excessive alcohol consumption is prevalent among adolescents and may result in lasting neurobehavioral consequences. The use of animal models to study adolescent alcohol exposure has the advantage of allowing for the control necessary in order to evaluate the effects of ethanol on the brain and separate such effects from genetic background and other environmental insults. In the present study the effects of moderate ethanol vapor exposure, during adolescence, on measures of neurogenesis and behavioral measures were evaluated at two different times following ethanol withdrawal, in adulthood. The two groups of Wistar rats were both exposed to intermittent ethanol vapor (14 hrs on/10 hrs off/day) for 35–36 days from PD 23-PD 58 (average blood ethanol concentration (BEC): 163 mg%). In the first group, after rats were withdrawal from vapor they were subsequently assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test and then sacrificed at 72 days of age. The second group of rats were withdrawn from vapor and injected for 5 days with Bromo-deoxy-Uridine (BrdU). Over the next 8 weeks they were also assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test and then sacrificed at 113/114 days of age. All rats were perfused for histochemical analyses. Ethanol vapor exposed rats displayed hypoactivity in tests of locomotion and less anxiety-like and/or more “disinhibitory” behavior in the open field conflict. Quantitative analyses of immunoreactivity revealed a significant reduction in measures of neurogenesis, progenitor proliferation, as indexed by doublecortin (DCX), Ki67, and increased markers of cell death as indexed by cleaved caspase-3, and Fluoro-Jade at 72 days, and decreases in doublecortin (DCX), and increases in cleaved caspase-3 at 114 days in the ethanol vapor exposed rats. Progenitor survival, as assessed by BrdU+, was reduced in the vapor exposed animals that were sacrificed at 114 days. The reduction seen in DCX labeled in cell counts was significantly correlated with hypoactivity at 24 hours after withdrawal as well as less anxiety-like and/or more “disinhibitory” behavior in the open field conflict test at 2 and 8 weeks following termination of vapor exposure. These studies demonstrate that behavioral measures of disinhibitory behavior correlated with decreases in neurogenesis are all significantly and persistently impacted by periadolescent ethanol exposure and withdrawal in Wistar rats.
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影响因子：
3.3
作者：
Anderson ML;Nokia MS;Govindaraju KP;Shors TJ
通讯作者：
Shors TJ
影响因子：
3.6
作者：
Crews, Fulton Timm;Boettiger, Charlotte Ann
通讯作者：
Boettiger, Charlotte Ann
影响因子：
--
作者：
EHLERS, CL;CHAPLIN, RI
通讯作者：
CHAPLIN, RI
影响因子：
3.5
作者：
Barha, Cindy K.;Brummelte, Susanne;Galea, Liisa A. M.
通讯作者：
Galea, Liisa A. M.
影响因子：
8.2
作者：
Balu, Darrick T.;Lucki, Irwin
通讯作者：
Lucki, Irwin