Inpp5f regulates CNS axon regeneration through phosphoinositide metabolism

描述（由申请人提供）：中枢神经系统（CNS）的创伤性损伤损害长距离投射轴突，并使突触前和突触后神经元断开。患者通常患有永久性神经功能缺损，因为在人类或其他哺乳动物中，切断的CNS轴突不能自发再生。了解限制CNS轴突再生的生物学机制为开发安全有效的治疗创伤性CNS损伤患者的疗法提供了希望。该提议旨在表征INPP5F（一种推定的CNS轴突再生抑制剂）在小鼠视神经挤压和脊髓背侧半切损伤后限制恢复中的作用。所提出的实验使用小鼠手术、免疫组织化学、生物化学、分子克隆和小鼠行为测定中的标准技术。此外，拟议的实验将证明一种新的技术，在成年小鼠体内视网膜电穿孔，在发现和解剖中枢神经系统轴突再生的遗传调控的效用。从该提案中产生的知识将有助于该领域评估INPP5F作为创伤性CNS损伤治疗中的候选治疗靶点的潜力。通过完成本建议中的实验提供的培训将是关键，以准备一个年轻的科学家在了解中枢神经系统损伤的神经生物学的独立职业生涯。

DESCRIPTION (provided by applicant): Traumatic injury to the Central Nervous System (CNS) damages long-distance projections axons and disconnects pre-synaptic and post-synaptic neurons. Patients often suffer from permanent neurological deficits because severed CNS axons do not regenerate spontaneously in humans or other mammals. Understanding biological mechanisms that limit CNS axon regeneration holds promise for development of safe and effective therapeutics to treat traumatic CNS injury patients. This proposal is designed to characterize the role of INPP5F, a putative suppressor of CNS axon regeneration, in limiting recovery after optic nerve crush and spinal cord dorsal hemisection injury in mice. The proposed experiments use standard techniques in mouse surgery, immunohistochemistry, biochemistry, molecular cloning, and mouse behavioral assays. In addition, the proposed experiments will demonstrate the utility of a novel technique, in vivo retinal electroporation in adult mice, in discovering and dissecting genetic regulation of CNS axon regeneration. Knowledge generated from this proposal will help the field to evaluate the potential of INPP5F as a candidate therapeutic target in traumatic CNS injury treatment. Training provided by completing experiments in this proposal will be pivotal to prepare a young scientist for an independent career in understanding the neurobiology of CNS injury.