Willis L, Quintero E M, Nelson M, Granholm A-Ch
Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, Charleston, SC 29425.
Cell Transplant. 2005 Jan;14(1):21-29. doi: 10.3727/000000005783983313.
Trophic factors have been found to play a significant role both in long-term survival processes and in more rapid and dynamic processes in the brain and spinal cord. However, little is known regarding the regulation of expression of growth factors, and how these proteins interact on a cell-to-cell basis. We have studied protein levels of one growth factor known to affect the noradrenergic innervation of the hippocampal formation, namely brain-derived neurotrophic factor (BDNF). The purpose of the present study was to determine if appropriate innervation or contact between the LC noradrenergic neurons and their target, the hippocampus, affects expression of this growth factor in either brain region. Fetal brain stem tissue, containing the LC, and hippocampal formation were dissected from embryonic day 17 rat fetuses and transplanted together or alone into the anterior chamber of the eye of adult Fisher 344 rats. The tissue was grown together for 6 weeks, after which the animals were sacrificed and ELISAs for BDNF were undertaken. Transplantation to the anterior chamber of the eye increased the expression of BDNF in the hippocampal but not the brain stem tissue, compared with levels observed in fetal and adult rats in vivo. In addition, double grafting with hippocampal tissue more than tripled BDNF levels in brain stem grafts and doubled BDNF levels in the hippocampal portion of double grafts compared with hippocampal single grafts. Triple grafts containing basal forebrain, hippocampus, and brain stem LC tissue increased brain stem and hippocampal BDNF levels even further. Colchicine treatment of LC-hippocampal double grafts gave rise to a significant decrease in hippocampal BDNF levels to levels seen in single hippocampal grafts, while only a partial reduction of BDNF levels was seen in the brain stem portion of the same double grafts treated with colchicine. The findings suggest that an appropriate hippocampal innervation or contact with its target tissues is essential for regulation of BDNF expression in the brain stem, and that retrograde transport of BDNF can occur between double grafted fetal tissues in oculo.
人们发现，营养因子在大脑和脊髓的长期存活过程以及更快速、动态的过程中都发挥着重要作用。然而，关于生长因子表达的调控以及这些蛋白质在细胞间如何相互作用，我们却知之甚少。我们研究了一种已知会影响海马结构去甲肾上腺素能神经支配的生长因子的蛋白质水平，即脑源性神经营养因子（BDNF）。本研究的目的是确定蓝斑去甲肾上腺素能神经元与其靶标海马体之间适当的神经支配或接触是否会影响这两个脑区中这种生长因子的表达。从胚胎第17天的大鼠胎儿中分离出包含蓝斑的胎儿脑干组织和海马结构，然后将它们一起或单独移植到成年Fisher 344大鼠的眼前房。这些组织共同生长6周，之后处死动物并进行BDNF的酶联免疫吸附测定。与在体内观察到的胎儿和成年大鼠中的水平相比，移植到眼前房增加了海马体而非脑干组织中BDNF的表达。此外，与海马单移植相比，与海马组织双移植使脑干移植中的BDNF水平增加了两倍多，双移植的海马部分中的BDNF水平增加了一倍。包含基底前脑、海马体和脑干蓝斑组织的三移植进一步提高了脑干和海马体中的BDNF水平。用秋水仙碱处理蓝斑 - 海马双移植导致海马体中BDNF水平显著降低至单海马移植中的水平，而在用秋水仙碱处理的同一双移植的脑干部分中仅观察到BDNF水平部分降低。这些发现表明，适当的海马神经支配或与其靶组织的接触对于脑干中BDNF表达的调控至关重要，并且BDNF的逆行运输可以在眼内双移植的胎儿组织之间发生。
