Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis.
Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis.
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DOI：
10.1016/j.neuroscience.2013.09.031
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发表时间：
2013-12-19
期刊：
影响因子：
3.3
通讯作者：
Woods J
中科院分区：
文献类型：
--
作者：
Briones TL;Woods J
在这里，我们调查了神经发生和BDNF表达的变化是否是可能的机制参与抑郁样症状在戒断/戒酒期间慢性酗酒模式饮酒后，鉴于有限的研究，解决这些因素之间的联系，在青少年大脑。研究中使用了47只雄性Sprague-Dawley大鼠，实验方案在大鼠25日龄时开始。将大鼠分配至：（a）乙醇组或（B）对照组。每组动物进一步随机接受：脑源性神经营养因子（BDNF）受体激动剂或溶剂。训练大鼠自我施用乙醇，并且暴饮暴食方案包括每天30分钟的实验会话，持续12天，持续4小时进入黑暗期。在最后一次饮酒后两天，在蔗糖偏好测试中测试大鼠以评估快感缺乏，并在习惯化后进行旷场测试以评估行为绝望。我们的数据显示：（1）以类似暴饮暴食的模式自我施用酒精会导致醉酒，如国家酒精滥用和酒精中毒研究所（NIAAA）所定义的，并且这种酒精暴露模式与抑郁样症状的发展相关;（2）两个乙醇组之间的血液酒精水平没有显著差异;（3）慢性酗酒导致抑郁表型的形成，海马神经前体细胞的存活率和神经元分化能力降低，戒断期BDNF的作用减弱。但我们研究中最重要的发现是，通过使用酪氨酸激酶受体B（Trk B，一种BDNF受体）激动剂增强BDNF的作用，恢复了神经发生，消除了戒断/戒酒期间观察到的酒精诱导的快感缺乏和绝望行为。我们的研究结果表明，脑源性神经营养因子可能是一个分子，可以有针对性的干预酗酒抑郁症的并发症。
Here we investigated whether changes in neurogenesis and BDNF expression are possible mechanisms involved in the depression-like symptom during the withdrawal/abstinence period after chronic binge-pattern alcohol consumption given the limited number of studies addressing the link between these factors in the adolescent brain. Forty-seven male Sprague-Dawley rats were used in the study and the experimental protocol started when rats were 25-days old. Rats were assigned to either: (a) ethanol or (b) control group. Animals in each group were further randomized to receive either: brain-derived neurotrophic factor (BDNF) receptor agonist or vehicle. Rats were trained to self-administer ethanol and the binge protocol consisted of daily 30-min experimental sessions 4 hours into the dark period for 12 days. Two days after the last drinking session, rats were tested in the sucrose preference test to evaluate anhedonia and the open field test after habituation to evaluate behavioral despair. Our data showed that: (1) self-administration of alcohol in a binge-like pattern causes inebriation as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and this pattern of alcohol exposure is associated with the development of depression-like symptom; (2) no significant difference in blood alcohol levels between the 2 ethanol groups; and (3) chronic binge drinking resulted in the development of depressive phenotype, decrease survival and neuronal differentiation of neural progenitor cells in the hippocampus, and decrease BDNF effect during the withdrawal period. But the most important finding in our study is that augmenting BDNF actions through the use of tyrosine kinase receptor B (TrkB, a BDNF receptor) agonist restored neurogenesis and abolished the alcohol-induced anhedonia and despair behaviors seen during the withdrawal/abstinence period. Our results suggest that BDNF might be a molecule that can be targeted for interventions in alcoholism–depression co-incidence.
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影响因子：
2.9
作者：
Hamilton GF;Murawski NJ;St Cyr SA;Jablonski SA;Schiffino FL;Stanton ME;Klintsova AY
通讯作者：
Klintsova AY
影响因子：
12.7
作者：
DEYKIN, EY;LEVY, JC;WELLS, V
通讯作者：
WELLS, V
影响因子：
2.8
作者：
Huang, Ming-Chyi;Chen, Chun-Hsin;Leu, Sy-Jye
通讯作者：
Leu, Sy-Jye
影响因子：
25
作者：
Imayoshi, Itaru;Sakamoto, Masayuki;Kageyama, Ryoichiro
通讯作者：
Kageyama, Ryoichiro
影响因子：
3.4
作者：
Couillard-Despres, S;Winner, B;Aigner, L
通讯作者：
Aigner, L