EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain

Enmanuel J. Perez, Maria L. Cepero, Sebastian U. Perez, Joseph T. Coyle, Thomas Sick, Daniel J Liebl

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalNeurobiology of Disease
Volume94
DOIs
StatePublished - Oct 1 2016

Fingerprint

Neuronal Plasticity
Synapses
Wounds and Injuries
Brain
Brain Concussion
Learning
Penetrating Wounds
Long-Term Potentiation
Receptor Protein-Tyrosine Kinases
Serine
Nervous System
Hippocampus
Traumatic Brain Injury
Proteins

Keywords

  • D-serine
  • EphB3 receptors
  • Synapse damage
  • Synaptic plasticity
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neurology

Cite this

EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain. / Perez, Enmanuel J.; Cepero, Maria L.; Perez, Sebastian U.; Coyle, Joseph T.; Sick, Thomas; Liebl, Daniel J.

In: Neurobiology of Disease, Vol. 94, 01.10.2016, p. 73-84.

Research output: Contribution to journalArticle

Perez, Enmanuel J. ; Cepero, Maria L. ; Perez, Sebastian U. ; Coyle, Joseph T. ; Sick, Thomas ; Liebl, Daniel J. / EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain. In: Neurobiology of Disease. 2016 ; Vol. 94. pp. 73-84.
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