Department of Molecular Pharmacology and Physiology, Johnnie B Byrd Sr Alzheimer's Center & Research Institute, University of South Florida Tampa, Florida 33612, USA.
Mol Neurodegener. 2009 May 27;4:21. doi: 10.1186/1750-1326-4-21.
The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR) mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP) is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.
载脂蛋白 E 受体系统在海马体中密切参与突触传递和可塑性的调节。特定载脂蛋白 E 同种型表达与人类神经退行性疾病的关联使人们关注这些载脂蛋白 E 同种型在脂蛋白受体依赖性突触调节中的作用。在本研究中，我们使用载脂蛋白 E2、载脂蛋白 E3 和载脂蛋白 E4 靶向替换 (TR) 小鼠以及重组人载脂蛋白 E 同种型来确定载脂蛋白 E 同种型在海马体 CA1 突触功能中的作用。虽然载脂蛋白 E 同种型对突触传递没有影响，但与载脂蛋白 E2 TR 小鼠相比，载脂蛋白 E4 TR 小鼠的长时程增强 (LTP) 明显增强。LTP 诱导的载脂蛋白 E 同种型依赖性差异需要 NMDA 受体功能，并且载脂蛋白 E 同种型表达改变 ERK 和 JNK 信号转导的激活。急性应用特定的载脂蛋白 E 同种型也会改变 LTP 诱导，同时降低 NMDA 受体介导的场电位。此外，急性载脂蛋白 E 同种型应用对 ERK 和 JNK 激活没有相同的影响。这些发现表明人类载脂蛋白 E 同种型对成年海马体突触可塑性具有特定的、同种型依赖性的影响，并突出了慢性载脂蛋白 E 同种型表达和急性载脂蛋白 E 同种型暴露之间的机制差异。
