EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain.
Traumatic brain injury (TBI), ranging from mild concussion to severe penetrating wounds, can involve brain regions that contain damaged or lost synapses in the absence of neuronal death. These affected regions significantly contribute to sensory, motor and/or cognitive deficits. Thus, studying the mechanisms responsible for synaptic instability and dysfunction is important for protecting the nervous system from the consequences of progressive TBI. Our controlled cortical impact (CCI) injury produces ~20% loss of synapses and mild changes in synaptic protein levels in the CA3-CA1 hippocampus without neuronal losses. These synaptic changes are associated with functional deficits, indicated by >50% loss in synaptic plasticity and impaired learning behavior. We show that the receptor tyrosine kinase EphB3 participates in CCI injury-induced synaptic damage, where EphB3(-/-) mice show preserved long-term potentiation and hippocampal-dependent learning behavior as compared with wild type (WT) injured mice. Improved synaptic function in the absence of EphB3 results from attenuation in CCI injury-induced synaptic losses and reduced d-serine levels compared with WT injured mice. Together, these findings suggest that EphB3 signaling plays a deleterious role in synaptic stability and plasticity after TBI.
The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Enmanuel J
EJ
Perez
The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Maria L
ML
Cepero
The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Sebastian U
SU
Perez
Harvard Medical School, Department of Psychiatry, McLean Hospital, Boston, MA 02115, USA.
Joseph T
JT
Coyle
Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
Thomas J
TJ
Sick
The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: dliebl@miami.edu.
Daniel J
DJ
Liebl
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D036223:Receptor, EphB3 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D036223:Receptor, EphB3
EphB3 receptors; Synapse damage; Synaptic plasticity; Traumatic brain injury; d-serine