Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus.
Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus.
复制标题
新生儿酒精暴露对大鼠视交叉上核血管活性肠多肽神经元的影响。
DOI：
10.1016/j.alcohol.2009.06.002
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Earnest,DavidJ
中科院分区：
文献类型：
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作者：
Farnell,YuhuaZ;Allen,GreggC;Neuendorff,Nichole;West,JamesR;Wei-Jung,AChen;Earnest,DavidJ
新生大鼠酒精暴露引起视交叉上核(SCN)的长期改变，这些改变可能是成年大鼠昼夜行为明暗调节紊乱的原因，包括光捕获模式、光-暗周期改变的重新捕获速率以及对光的相移反应。由于含有血管活性肠多肽(VIP)的SCN神经元通过视网膜下丘脑束直接接受光输入，从而在光对SCN时钟机制的昼夜调节中发挥重要作用，因此本研究观察了新生大鼠酒精暴露对成年大鼠SCN内VIP神经元数量的长期影响。采用人工饲养的方法，在出生后第4~9天，用酒精(3.0、4.5或6.0g/kg/d)或等热量奶粉(胃造口对照；GC)饲养雄性SD大鼠。在2-3月龄时，金银花对照组(SC)、GC组和EtoH组动物暴露于恒定黑暗(DD)中，取SCN组织，用定量聚合酶链式反应(PCR)和原位杂交分析VIP mRNA的表达，或用体视学方法分析VIP免疫反应(Ir)神经元。新生大鼠酒精暴露对VIP mRNA的表达没有影响，但显著改变了成年大鼠SCN内含有该肽的神经元的免疫染色。在所有对照组和乙醇处理组中，VIP mRNA的相对丰度和表达该转录本的神经元的解剖分布相似。然而，与两对照组相比，每天6.0g/kg酒精暴露组大鼠SCN内VIP-ir神经元的总数和密度显著减少约35%。这些结果表明，在脑发育过程中，SCN内的VIP神经元群体容易受到乙醇诱导的损伤。观察到的含血管活性肠肽的SCN神经元的变化可能会影响对光输入的时钟反应，从而有助于新生儿酒精暴露对昼夜行为的光调节的长期影响。
Neonatal alcohol exposure produces long-term changes in the suprachiasmatic nucleus (SCN) that are presumably responsible for disturbances in the light–dark regulation of circadian behavior in adult rats, including the pattern of photoentrainment, rate of re-entrainment to shifted light–dark cycles, and phase-shifting responses to light. Because SCN neurons containing vasoactive intestinal polypeptide (VIP) receive direct photic input via the retinohypothalamic tract and thus play an important role in the circadian regulation of the SCN clock mechanism by light, the present study examined the long-term effects of neonatal alcohol exposure on VIP neuronal populations within the SCN of adult rats. Male Sprague-Dawley rat pups were exposed to alcohol (EtOH; 3.0, 4.5, or 6.0g/kg/day) or isocaloric milk formula (gastrostomy control; GC) on postnatal days 4–9 using artificial-rearing methods. At 2–3 months of age, animals from the suckle control (SC), GC, and EtOH groups were exposed to constant darkness (DD) and SCN tissue was harvested for subsequent analysis of either VIP mRNA expression by quantitative polymerase chain reaction (PCR) and in situ hybridization or of VIP-immunoreactive (ir) neurons using stereological methods. Neonatal alcohol exposure had no impact on VIP mRNA expression but dramatically altered immunostaining of neurons containing this peptide within the SCN of adult rats. The relative abundance of VIP mRNA and anatomical distribution of neurons expressing this transcript were similar among all control- and EtOH-treated groups. However, the total number and density of VIP-ir neurons within the SCN were significantly decreased by about 35% in rats exposed to alcohol at a dose of 6.0g/kg/day relative to that observed in both control groups. These results demonstrate that VIP neuronal populations in the SCN are vulnerable to EtOH-induced insult during brain development. The observed alterations in SCN neurons containing VIP may have an impact upon clock responses to light input and thus contribute to the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior.