Falkenberg T, Metsis M, Timmusk T, Lindefors N
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1993 Dec;57(4):891-6. doi: 10.1016/0306-4522(93)90034-d.
Developmental or degenerative damage of the neuronal architecture in the entorhinal cortex may disintegrate a functional part of hippocampal input since the entorhinal cortex provides a major source of neocortical and subcortical input to the hippocampus. These alterations, such as seen in Alzheimer's disease, schizophrenia and temporal lobe epilepsy are likely to be associated with cognitive deficits. To understand the basis for pathological changes in the corticohippocampal loop it is important to study mechanisms involved in neuronal plasticity. Brain-derived neurotrophic factor provides a possible substrate to mediate such plasticity. We have previously provided evidence that stimulation of hippocampal afferents transynaptically increase the level of brain-derived neurotrophic factor messenger RNA within the hippocampus. In the present study we have investigated whether different brain-derived neurotrophic factor messenger RNAs are specifically regulated in the hippocampus. We provide evidence for a differential and dose-dependent regulation of the different brain-derived neurotrophic factor promoters in the hippocampus by afferents in the entorhinal cortex. Our finding of a graded regulation is in contrast to earlier evidence of an "all-or-none" type of regulation.
内嗅皮质中神经元结构的发育性或退行性损伤可能会瓦解海马体输入的一个功能部分，因为内嗅皮质是海马体新皮质和皮质下输入的主要来源。这些改变，如在阿尔茨海默病、精神分裂症和颞叶癫痫中所见，可能与认知缺陷有关。为了理解皮质 - 海马回路病理变化的基础，研究神经元可塑性所涉及的机制很重要。脑源性神经营养因子提供了一种可能介导这种可塑性的底物。我们之前已经提供证据表明，海马体传入神经的刺激通过突触传递增加了海马体内脑源性神经营养因子信使核糖核酸的水平。在本研究中，我们调查了不同的脑源性神经营养因子信使核糖核酸在海马体中是否受到特异性调节。我们提供证据表明，内嗅皮质中的传入神经对海马体中不同的脑源性神经营养因子启动子进行差异和剂量依赖性调节。我们关于分级调节的发现与早期“全或无”类型调节的证据形成对比。
