ACTIVITY DEPENDENT PLASTICITY OF NEUROENDOCRINE AXONS

神经内分泌轴突的活动依赖性可塑性

• 批准号: 6650793
• 负责人: CHARLES M PADEN
• 金额: $ 22.99万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650793
• 关键词: afferent nerve; albino rat; axon; confocal scanning microscopy; developmental neurobiology; glutamates; growth factor receptors; hypothalamus; immunocytochemistry; in situ hybridization; insulinlike growth factor; interleukin 1; neural plasticity; neuroendocrine system; neuronal guidance; neurotrophic factors; norepinephrine; polymerase chain reaction

DESCRIPTION (applicant's abstract): The long term objectives of this project are: 1) to determine the mechanisms that link neuronal activity to axonal sprouting in the adult CNS; 2) to discover the cause of maturational decrements in axonal sprouting; and 3) to examine potential means of compensating for these decrements. These objectives will be addressed using a model neuroendocrine system that displays unusually vigorous axonal plasticity, the hypothalamic magnocellular neurosecretory system, or MNS. Uninjured neurons in the MNS of young adult (35 day-old) rats undergo robust collateral axonal sprouting in response to a lesion that destroys the contralateral side of this bilateral system. This sprouting response is activity-dependent. MNS neurons are hyperactive during axonal sprouting, secreting more of the neuropeptides oxytocin and vasopressin, while simultaneously sprouting new axon collaterals that reestablish the neurosecretory axon population within the neurohypophysis. Sprouting does not occur if activity of MNS neurons is inhibited by establishment of a chronic hyposmolar state, and MNS neurons in more mature (125 day-old) rats do not become hyperactive in response to the lesion and do not sprout. The specific aims of the proposal are: 1) to determine if it is the initiation and/or the maintenance of the growth process that is activity-dependent, and to examine the role of glutamatergic and noradrenergic afferents in stimulating sprouting; 2) to determine if activity-dependent axonal sprouting is mediated by the growth factors IGF-I, CNTF, and BDNF and the cytokine IL-1beta, synthesized by and acting upon the neurons and glia of the MNS; and 3) to identify mechanisms responsible for the maturational decline in collateral sprouting and to determine if chronic hyperosmotic stimulation of MNS neurons can reverse this decline. These aims will be accomplished by altering MNS activity by receptor blockade or through chronic osmostimulation and correlating changes in the expression, cellular localization, and activity of the above factors and their receptors with the extent of axonal sprouting in animals of different ages. Fulfillment of these aims will provide new insights regarding the cellular mechanisms involved in reestablishment of axon populations in the injured brain and the alterations that occur in these mechanisms during brain maturation.

描述（申请人摘要）：本项目的长期目标 主要是：1）确定神经元活动与轴突活动之间的联系机制， 2）发现成熟衰退的原因 在轴突发芽;和3）检查潜在的补偿手段， 这些减少。这些目标将通过一个模型来实现 神经内分泌系统表现出异常旺盛的轴突可塑性， 下丘脑大细胞神经分泌系统（MNS）。未受伤的神经元 年轻成年大鼠（35日龄）MNS经历了强健的侧支轴突 在对破坏对侧的损伤的反应中发芽， 双边系统。这种发芽反应是活动依赖性的。MNS神经元 在轴突发芽时过度活跃，分泌更多的神经肽 催产素和加压素，同时萌发新的轴突侧支 在神经垂体内重建神经分泌轴突群。 如果MNS神经元的活性被抑制，则不会发生发芽。 建立慢性低磨牙状态，且MNS神经元较成熟 (125日龄）大鼠对损伤的反应不会变得过度活跃， 而不是发芽该提案的具体目的是：1）确定它是否是 启动和/或维持生长过程， 活性依赖性，并检查β-amatergic和去甲肾上腺素能的作用 刺激发芽的传入神经; 2）确定活动依赖性 轴突发芽由生长因子IGF-I、CNTF和BDNF介导， 细胞因子IL-1 β，由神经元和神经胶质合成并作用于神经元和神经胶质， MNS; 3）确定成熟下降的机制 并确定慢性高渗刺激是否 MNS神经元可以逆转这种下降。这些目标将通过以下方式实现： 通过受体阻断或通过慢性渗透刺激改变MNS活性 并关联表达、细胞定位和活性的变化， 上述因子及其受体与轴突出芽程度的关系 不同年龄的动物。实现这些目标将提供新的见解 关于轴突重建的细胞机制 受伤的大脑中的细胞群以及这些细胞群中发生的变化， 大脑成熟的机制。

项目成果

Axons containing the growth associated protein GAP-43 specifically target rat corticotrophs following adrenalectomy.

含有生长相关蛋白 GAP-43 的轴突专门针对肾上腺切除术后的大鼠促肾上腺皮质激素。

• DOI: 10.1046/j.1365-2826.1998.00252.x
• 发表时间: 1998
• 期刊: Journal of neuroendocrinology
• 影响因子: 3.2
• 作者: Paden,CM;Babcock,C;Conner,KA;Duong,DK;Kuhl,JM
• 通讯作者: Kuhl,JM

Evidence that IGF-I acts as an autocrine/paracrine growth factor in the magnocellular neurosecretory system: neuronal synthesis and induction of axonal sprouting.

IGF-I 在大细胞神经分泌系统中作为自分泌/旁分泌生长因子的证据：神经元合成和轴突萌芽的诱导。

• DOI: 10.1006/exnr.1999.7189
• 发表时间: 1999
• 期刊: Experimental neurology.
• 作者: Zhou,X;Herman,JP;Paden,CM
• 通讯作者: Paden,CM

Ciliary neurotrophic factor is expressed in the magnocellular neurosecretory system of the rat in vivo: evidence for injury- and activity-induced upregulation.

睫状神经营养因子在大鼠体内的大细胞神经分泌系统中表达：损伤和活动诱导上调的证据。

• DOI: 10.1016/j.expneurol.2005.09.009
• 发表时间: 2006
• 期刊: Experimental neurology.
• 作者: Watt,JohnA;Bone,Sven;Pressler,Mandy;Cranston,HarwoodJ;Paden,CharlesM
• 通讯作者: Paden,CharlesM

Central peptidergic neurons are hyperactive during collateral sprouting and inhibition of activity suppresses sprouting.

中枢肽能神经元在侧支萌芽期间过度活跃，抑制活性会抑制萌芽。

• DOI: 10.1523/jneurosci.19-05-01586.1999
• 发表时间: 1999
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Watt,JA;Moffet,CW;Zhou,X;Short,S;Herman,JP;Paden,CM
• 通讯作者: Paden,CM

Upregulation of the p75 low-affinity neurotrophin receptor by phagocytically active perivascular active cells in the rat neural lobe.

大鼠神经叶中具有吞噬活性的血管周围活性细胞对 p75 低亲和力神经营养素受体的上调。

• DOI: 10.1007/s004410000295
• 发表时间: 2001
• 期刊: Cell and tissue research
• 影响因子: 3.6
• 作者: Watt,JA;Paden,CM
• 通讯作者: Paden,CM