Emergence of NMDAR-independent long-term potentiation at hippocampal CA1 synapses following early adolescent exposure to chronic intermittent ethanol: role for sigma-receptors.
Emergence of NMDAR-independent long-term potentiation at hippocampal CA1 synapses following early adolescent exposure to chronic intermittent ethanol: role for sigma-receptors.
复制标题
青少年早期接触慢性间歇性乙醇后海马 CA1 突触出现不依赖 NMDAR 的长期增强：西格玛受体的作用。
DOI：
10.1002/hipo.20379
复制
发表时间：
2008
期刊：
影响因子：
3.5
通讯作者：
Gruol,DonnaL
中科院分区：
文献类型：
--
作者：
Sabeti,Jilla;Gruol,DonnaL
酗酒的青少年比成年人更容易出现记忆障碍。记忆障碍通常涉及海马神经元建立兴奋性神经传递长期增强（LTP）能力的改变；然而，很少有研究探讨青春期长期接触乙醇如何影响海马的 LTP 机制。我们研究了在青春期早期（即青春期前）或青春期后期（即青春期后）发育期间暴露于令人中毒浓度的慢性间歇性乙醇（CIE）蒸气的大鼠海马切片中 LTP 机制的变化。在停止空气（对照）或 CIE 蒸汽治疗后 24 小时，对海马切片中兴奋性 CA1 突触的 LTP 进行评估。对照切片中的 CA1 突触在高频刺激诱导后表现出稳定的 LTP，这完全依赖于 NMDAR 功能。相比之下，青春期早期 CIE 暴露动物的切片显示出一种复合形式的 LTP，由 NMDAR 依赖性成分和独立于 NMDAR 的缓慢发育成分组成。这些成分相加得出的 LTP 远远高于年龄匹配对照切片中的 LTP 水平。浴液应用 σ 受体拮抗剂 BD1047 和神经活性类固醇孕烯醇酮硫酸盐（而非急性乙醇应用）可阻断 NMDAR 依赖性 LTP，同时保持 NMDAR 依赖性 LTP 完整。对 NMDAR 独立 LTP 诱导过程中突触前功能的分析表明，在青春期早期 CIE 暴露动物的切片中，通过 σ 受体依赖性机制增强了突触前功能。相比之下，青春期后期动物青春期开始后暴露于 CIE 会导致 LTP 水平下降。 σ受体和神经活性类固醇在不依赖于 NMDAR 的 LTP 发展中的作用的确定表明，海马突触可塑性（也许还有记忆）可能通过青少年发育前阶段的长期乙醇暴露而发生独特的改变。 © 2007 Wiley-Liss, Inc.
Adolescent humans who abuse alcohol are more vulnerable than adults to the development of memory impairments. Memory impairments often involve modifications in the ability of hippocampal neurons to establish long‐term potentiation (LTP) of excitatory neurotransmission; however, few studies have examined how chronic ethanol exposure during adolescence affects LTP mechanisms in hippocampus. We investigated changes in LTP mechanisms in hippocamal slices from rats exposed to intoxicating concentrations of chronic intermittent ethanol (CIE) vapors in their period of early‐adolescent (i.e., prepubescent) or late‐adolescent (i.e., postpubescent) development. LTP was evaluated at excitatory CA1 synapses in hippocampal slices at 24 h after the cessation of air (control) or CIE vapor treatments. CA1 synapses in control slices showed steady LTP following induction by high‐frequency stimulation, which was fully dependent on NMDAR function. By contrast, slices from early‐adolescent CIE exposed animals showed a compound form of LTP consisting of an NMDAR‐dependent component and a slow‐developing component independent of NMDARs. These components summated to yield LTP of robust magnitude above LTP levels in age‐matched control slices. Bath‐application of the σ‐receptor antagonist BD1047 and the neuroactive steroid pregnenolone sulfate, but not acute ethanol application, blocked NMDAR‐independent LTP, while leaving NMDAR‐dependent LTP intact. Analysis of presynaptic function during NMDAR‐independent LTP induction demonstrated increased presynaptic function via a σ‐receptor‐dependent mechanism in slices from early‐adolescent CIE‐exposed animals. By contrast, CIE exposure after puberty onset in late‐adolescent animals produced decrements in LTP levels. The identification of a role for σ‐receptors and neuroactive steroids in the development of NMDAR‐independent LTP suggests an important pathway by which hippocampal synaptic plasticity, and perhaps memory, may be uniquely altered by chronic ethanol exposure during the prepubescent phase of adolescent development. © 2007 Wiley‐Liss, Inc.