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.

Public Health Relevance

Traumatic injury to the Central Nervous System (CNS) is a devastating medical condition to patients and a huge healthcare cost burden to society. One promising strategy to promote recovery of neurological functions after traumatic CNS injury is to promote regeneration of damaged CNS axons. This proposal will investigate the potential of inactivating INPP5F as a novel therapeutic approach to encourage CNS axon regeneration and functional recovery in mouse models of traumatic CNS injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS081953-02
Application #
8695121
Study Section
Special Emphasis Panel (ZRG1-F03A-N (20))
Program Officer
Jakeman, Lyn B
Project Start
2013-06-16
Project End
2015-06-15
Budget Start
2014-06-16
Budget End
2015-06-15
Support Year
2
Fiscal Year
2014
Total Cost
$28,716
Indirect Cost
Name
Yale University
Department
None
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520