Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life.
Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life.
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青春期慢性间歇性乙醇暴露会产生焦虑和认知的性别和年龄依赖性变化，而不会在生命后期改变小胶质细胞的反应性。
DOI：
10.3389/fnbeh.2023.1223883
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发表时间：
2023
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
作者：
在动物模型中，青少年时期的酒精暴露已被证明会产生长期持久的影响，包括可持续到成年早期的焦虑样行为和可持续大部分寿命的认知障碍。然而，很少有研究调查，如果在青春期暴饮暴食的酒精暴露产生持续的焦虑样行为，并伴随着损害认知晚年的生活。此外，很少有研究调查这种行为的影响，在雌性和雄性大鼠的寿命。最后，青春期的酒精暴露是否会改变生命后期相关大脑区域的小胶质细胞激活，这一点还有待确定。在本研究中，在接下来的18个月内，在高架十字迷宫和旷场任务中进行测试之前，将雌性和雄性青春期大鼠以慢性间歇模式暴露于3.0或5.0 g/kg乙醇或水对照。然后通过Morris水迷宫在空间参考任务中训练动物，然后测试它们的行为灵活性。最后，取出脑，切片，并使用放射自显影法测定[3 H] PK 11195结合的假定小胶质细胞活化。男性，但不是女性，表现出焦虑样表型，最初在慢性间歇性乙醇暴露范式，解决在成年期。此外，男性而不是女性在晚年改变了空间参考学习和行为灵活性受损。相反，[3 H] PK 11195结合率在女性中显著高于男性，并且小胶质细胞活化水平作为性别和大脑区域的函数相互作用，但没有与青少年酒精暴露相关的长期结果。这些数据进一步证实，在青春期饮酒过量会导致行为改变，这种改变可以持续整个生命周期。此外，这些数据表明，在青春期之前的酗酒样乙醇暴露不会加剧生命后期的小胶质细胞激活，但这种表达在整个生命周期中具有性别和大脑区域依赖性。
Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [3H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [3H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.
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影响因子：
2.9
作者：
JOHNSTON, AL;FILE, SE
通讯作者：
FILE, SE
影响因子：
3.6
作者：
Coleman, Leon Garland, Jr.;Liu, Wen;Oguz, Ipek;Styner, Martin;Crews, Fulton T.
通讯作者：
Crews, Fulton T.
影响因子：
4.1
作者：
Ho, Ada Man-Choi;Peyton, Mina P.;Scaletty, Samantha J.;Trapp, Sarah;Schreiber, Areonna;Madden, Benjamin J.;Choi, Doo-Sup;Matthews, Douglas B.
通讯作者：
Matthews, Douglas B.
DOI：
10.1016/j.bbi.2015.10.003
发表时间：
2016-02
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Bollinger JL;Bergeon Burns CM;Wellman CL
通讯作者：
Wellman CL
影响因子：
3.3
作者：
Fernandez GM;Lew BJ;Vedder LC;Savage LM
通讯作者：
Savage LM