SYNAPSINS AND ANIMAL MODELS OF SYNAPTOGENESIS

突触蛋白是一类脑特异性突触囊泡富集蛋白， 通过束缚调节神经递质释放的磷蛋白 突触囊泡到活动区。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 突触蛋白加速轴突的伸长和 突触，而缺乏突触的神经元培养物具有延迟的 轴突伸长和突触的速率。为了确定突触蛋白是否作为 在体内的营养剂，我们将检查小鼠缺乏各种 突触蛋白我们将比较突触形成的速度和程度， 野生型和突触蛋白缺陷小鼠。我们亦会研究 突触蛋白缺陷小鼠中突触随年龄增长而丧失的程度。海马 CA 1锥体神经元经历周期性树突棘发芽和修剪 在发情期间和雌激素引发之后。目前的研究将 试图确定缺乏突触蛋白的雌性小鼠是否会经历类似的程度， 突触发生的过程实验将检查颗粒细胞苔藓纤维 伴随点燃的发芽，癫痫的实验模型， 缺乏突触蛋白的老鼠发芽的程度将被量化， 在野生型和突触蛋白缺陷小鼠之间进行比较。研究将 检查血清素能纤维再生的速率和程度， 野生型和突触蛋白缺陷小鼠的化学损伤。研究 表明某些神经营养剂的至少一些作用 (e.g.神经生长因子和脑源性神经营养因子）可能通过突触蛋白介导， 再生血清素轴突的生长因子刺激也将 在突触蛋白缺陷小鼠中进行评估。内嗅神经损伤后 皮质，来自对侧穿支通路的轴突侧支， 使去传入的齿状回受神经支配。这种再生对 营养因子和行为相关。我们会研究 野生型和突触蛋白的组织再生和行为恢复， 缺陷小鼠后病变的内嗅皮质。最后，年龄- 依赖性行为缺陷将在野生型和突触蛋白中进行比较， 缺陷小鼠这些研究应确定的营养作用， 成年动物中的突触蛋白，并为未来的研究奠定基础。 旨在阐明突触素作用机制的研究， 利用这种营养作用治疗阿尔茨海默病。

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.