Hamilton G F, Hernandez I J, Krebs C P, Bucko P J, Rhodes J S
Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Neuroscience. 2017 Jun 3;352:52-63. doi: 10.1016/j.neuroscience.2017.03.058. Epub 2017 Apr 6.
Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. Male C57BL/6J mice received either saline or 5g/kg ethanol (two doses, two hours apart) on PD 5, 7, and 9. On PD 35, animals received a running wheel or remained sedentary for 48days before behavioral testing and perfusion on PD 83. The number of PV+ interneurons was stereologically measured in three separate mPFC subregions: infralimbic, prelimbic and anterior cingulate cortices (ACC). Neonatal alcohol exposure decreased number of PV+ interneurons and volume of the ACC, but the other regions of the mPFC were spared. Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.
发育期酒精暴露会导致一系列认知和神经解剖学异常，其中之一是内侧前额叶皮质（mPFC）损伤导致的执行功能受损。本研究确定了相当于孕晚期的酒精暴露是否会减少mPFC中γ-氨基丁酸能小白蛋白阳性（PV+）中间神经元的数量，据推测这些神经元在mPFC的局部抑制中起重要作用。还探讨了其对被动回避学习的影响以及成年期有氧运动的治疗作用。雄性C57BL/6J小鼠在出生后第5、7和9天接受生理盐水或5g/kg乙醇（分两剂，间隔两小时）。在出生后第35天，动物接受跑步轮或保持久坐48天，然后在出生后第83天进行行为测试和灌注。采用立体定位法测量了mPFC三个不同亚区域（边缘下皮质、边缘前皮质和前扣带回皮质（ACC））中PV+中间神经元的数量。新生儿酒精暴露减少了PV+中间神经元的数量和ACC的体积，但mPFC的其他区域未受影响。酒精损害了被动回避的习得，但不影响其记忆恢复，并且对转棒试验中的运动表现没有影响。运动对PV+细胞数量、mPFC体积或被动回避的习得没有影响，但在对照组和酒精暴露组中均增强了记忆恢复，并且提高了对照组小鼠在转棒试验中的表现。结果支持以下假设：与发育期酒精暴露相关的部分行为缺陷是由于ACC中PV+中间神经元减少所致，但遗憾的是，运动似乎无法逆转这些缺陷中的任何一种。
