SYNAPSINS AND ANIMAL MODELS OF SYNAPTOGENESIS

它们是一个富含脑特异性突触小泡的家族 通过拴系调节神经递质释放的磷酸蛋白 突触小泡至活动区。最近，各种体外研究 已经表明，这些分子也有营养作用 轴突的延长和突触的形成。.的存在 突触素加速轴突的延长和神经节细胞的形成 突触，而培养缺乏突触的神经元具有迟缓 轴突延长率和突触。为了确定突触蛋白是否起到 在体内营养剂，我们将检查小鼠缺乏的各种 突触蛋白。我们将比较突触形成的速度和程度 野生型和突触素缺陷小鼠。我们还将研究 突触素缺陷小鼠突触丢失程度随年龄增长。海马区 CA1区锥体神经元经历树突棘的周期性萌发和修剪 在发情期间和之后的雌激素启动。目前的研究将 试图确定缺乏突触素的雌性小鼠是否会经历类似的程度 关于突触发生的。实验将检查颗粒细胞苔藓纤维 发芽伴随点燃，一种癫痫的实验模型，在 缺乏突触素的小鼠。发芽的程度将被量化并 野生型和突触素缺陷小鼠之间的比较。研究将会 术后检查血清能纤维再生的速度和程度 野生型和突触素缺陷小鼠的化学损伤。研究 表明某些神经营养剂的至少部分作用 (例如，NGF和BDNF)可能是通过突触蛋白介导的， 再生5-羟色胺轴突对生长因子的刺激也将 在突触素缺陷小鼠身上进行评估。在内脏受损后 皮质，来自对侧穿支路径的轴突侧支和 支配去传入的齿状突起。这种再生对 营养因子，并与行为相关。我们将研究 野生型和突触素的组织学再生和行为恢复 内嗅皮层损伤后的缺陷小鼠。最后，年龄-- 将野生型和突触素依赖的行为缺陷进行比较- 有缺陷的小鼠。这些研究应该建立起营养作用 成年动物中的突触蛋白，应该为未来奠定基础 旨在阐明突触素作用机制的研究以及在 在阿尔茨海默氏症中利用这种营养作用。

They synapsins are a family of brain-specific synaptic vesicle-enriched phosphoproteins that regulate neurotransmitter release by tethering synaptic vesicle to active zones. Recently a variety of in vitro studies have indicated that these molecules also have trophic effects on the elongation on axons and the formation of synapses. The presence of synapsins accelerates the elongation of axons and the formation of synapses, while cultures of neurons lacking the synapses have a retarded rate of axon elongation and synapses. To determine if the synapsins act as trophic agents in vivo, we will examine mice lacking the various synapsins. We will compare the rate and degree of synapse formation in wild-type and synapsin-deficient mice. We will also examine changes in the degree of synapse loss with aging in synapsin-deficient mice. Hippocampal CA1 pyramidal neurons undergo cyclic dendritic spine sprouting and pruning during oestrus and following estrogen priming. The present studies will seek to determine if female mice lacking synapsins undergo similar degrees of synaptogenesis. Experiments will examine the granule cell mossy fiber sprouting that accompanies kindling, an experimental model of epilepsy, in mice lacking synapsin. The degree of sprouting will be quantified and compared between wild-type and synapsin-deficient mice. Studies will examine the rate and degree of sertonergic fiber regeneration following chemical lesions in wild-type and synapsin-deficient mice. Studies indicate that at least some of the actions of certain neurotrophic agents (e.g. NGF and BDNF) may be mediated through the synapsins, the response of regenerating serotonin axons to growth factor stimulation will also be assessed in synapsin-deficient mice. Following lesioning of the entorhinal cortex, axons from the contralateral perforant path collateralize and innervate the deafferented dentate. This regeneration is sensitive to trophic factors and has behavioral correlates. We will examine the histological regrowth and behavioral recovery of wild-type and synapsin- deficient mice following lesions of the entorhinal cortex. Finally, age- dependent behavioral deficits will be compared in wild-type and synapsin- deficient mice. These studies should establish the trophic role of the synapsins in adult animals and should lay the groundwork for future studies aimed at elucidating the mechanisms of synapsin actions and at harnessing this trophic action in Alzheimer's disease.