Acute Axonal Degeneration Drives Development of Cognitive, Motor, and Visual Deficits after Blast-Mediated Traumatic Brain Injury in Mice.
Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain (WldS) of mice is resistant to some forms of axonal degeneration because of a triplicated fusion gene encoding the first 70 amino acids of Ufd2a, a ubiquitin-chain assembly factor, that is linked to the complete coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMAT1). Here, we demonstrate that resistance ofWldSmice to axonal degeneration after blast-mediated TBI is associated with preserved function in hippocampal-dependent spatial memory, cerebellar-dependent motor balance, and retinal and optic nerve-dependent visual function. Thus, early axonal degeneration is likely a critical driver of subsequent neurobehavioral complications of blast-mediated TBI. Future therapeutic strategies targeted specifically at mitigating axonal degeneration may provide a uniquely beneficial approach to treating patients suffering from the effects of blast-mediated TBI.
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Terry C
0000-0001-8460-1249
TC
Yin
Department of Psychiatry, Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Jaymie R
JR
Voorhees
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Rachel M
RM
Genova
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Kevin C
0000-0002-0258-077X
KC
Davis
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Ashley M
0000-0002-7712-6870
AM
Madison
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Jeremiah K
JK
Britt
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Coral J
0000-0003-2160-4244
CJ
Cintrón-Pérez
Department of Psychiatry, University of Iowa Carver College of Medicine , Iowa City, IA 52242.
Latisha
L
McDaniel
Department of Veteran Affairs Center for the Prevention and Treatment of Visual Loss, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
Matthew M
MM
Harper
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Department of Free Radical and Radiation Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Department of Veteran Affairs, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Weill Cornell Autism Research Program, Weill Cornell Medicine, Cornell University, New York, NY 10065.
Andrew A
AA
Pieper
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D001753:Blast Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D000070642:Brain Injuries, Traumatic / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D003071:Cognition; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning; D008817:Mice, Mutant Strains; D009043:Motor Activity; D000066829:Neuroprotection; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D065852:Spatial Memory; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014786:Vision Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D014796:Visual Perception; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology
C471292:Ube4b protein, mouse; D044767:Ubiquitin-Protein Ligases
WldS mouse; axonal degeneration; neurodegeneration; nicotinamide adenine dinucleotide; traumatic brain injury