Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats.
Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats.
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DOI：
10.1016/j.neuroscience.2017.02.045
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发表时间：
2017-04-21
期刊：
影响因子：
3.3
通讯作者：
Savage LM
中科院分区：
文献类型：
--
作者：
Fernandez GM;Lew BJ;Vedder LC;Savage LM
慢性间歇性暴露于乙醇（EtOH； CIE）会产生类似狂欢的中毒水平，这与认知功能的年龄依赖性缺陷有关。雄性Sprague-Dawley大鼠从青春期早期（出生后28天[PD]）、青春期中期（PD35）和成年期（PD72）三个年龄开始暴露于CIE （5 g/kg, 25% EtOH， 13次灌胃）。在实验1中，大鼠在CIE后进行行为测试。空间记忆不受CIE影响，但成年CIE大鼠在获得非空间辨别任务和随后的反转任务时受到损害。在青春期早期或中期暴露于CIE的大鼠在第一次逆转时受损，表现出短暂的行为灵活性损伤。血EtOH浓度与逆向任务的表现呈负相关。实验2检测了四个时间点额叶皮质（FC）和海马（HPC）内脑源性神经营养因子（BNDF）水平的变化：中毒期间、最终接触EtOH后24小时（急性戒断）、戒断后3周（恢复）和行为测试后。在任何时间点，CIE均未影响HPC BDNF水平。在中毒期间，BDNF在FC中被抑制，与暴露年龄无关。然而，在急性戒断期间，早期青春期CIE大鼠的FC BDNF水平持续降低，而成年CIE大鼠的BDNF水平则有所增加。恢复后，所有CIE大鼠的神经营养因子水平均恢复。我们的研究结果表明，间歇性暴饮暴食的EtOH暴露会导致FC BDNF水平的急性中断和长期的行为缺陷。然而，认知障碍的类型和持续时间取决于接触的年龄。
Chronic intermittent exposure to ethanol (EtOH; CIE) that produces binge-like levels of intoxication has been associated with age-dependent deficits in cognitive functioning. Male Sprague-Dawley rats were exposed to CIE (5 g/kg, 25% EtOH, 13 intragastric gavages) beginning at three ages: early adolescence (postnatal day [PD] 28), mid-adolescence (PD35) and adulthood (PD72). In experiment 1, rats were behaviorally tested following CIE. Spatial memory was not affected by CIE, but adult CIE rats were impaired at acquiring a non-spatial discrimination task and subsequent reversal tasks. Rats exposed to CIE during early or mid-adolescence were impaired on the first reversal, demonstrating transient impairment in behavioral flexibility. Blood EtOH concentrations negatively correlated with performance on reversal tasks. Experiment 2 examined changes in brain derived neurotrophic factor (BNDF) levels within the frontal cortex (FC) and hippocampus (HPC) at four time points: during intoxication, 24-hrs after the final EtOH exposure (acute abstinence), 3-weeks following abstinence (recovery) and after behavioral testing. HPC BDNF levels were not affected by CIE at any time point. During intoxication, BDNF was suppressed in the FC, regardless of the age of exposure. However, during acute abstinence, reduced FC BDNF levels persisted in early adolescent CIE rats, whereas adult CIE rats displayed an increase in BDNF levels. Following recovery, neurotrophin levels in all CIE rats recovered. Our results indicate that intermittent binge-like EtOH exposure leads to acute disruptions in FC BDNF levels and long-lasting behavioral deficits. However, the type of cognitive impairment and its duration differ depending on the age of exposure.