title: Mechanisms of dendritic spine remodeling in a rat model of traumatic brain injury.
abstract: Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. Calcium dysregulation could affect the activity of the calcium-sensitive phosphatase calcineurin (CaN), with serious implications for neural function. The present study used both an in vitro enzymatic assay and Western blot analyses to characterize the effects of lateral fluid percussion injury on CaN activity and CaN-dependent signaling in the rat forebrain. TBI resulted in an acute alteration of CaN phosphatase activity and long-lasting alterations of its downstream effector, cofilin, an actin-depolymerizing protein. These changes occurred bilaterally in the neocortex and hippocampus, appeared to persist for hours after injury, and coincided with synapse degeneration, as suggested by a loss of the excitatory post-synaptic protein PSD-95. Interestingly, the effect of TBI on cofilin in some brain regions was blocked by a single bolus of the CaN inhibitor FK506, given 1 h post-TBI. Overall, these findings suggest a loss of synapse stability in both hemispheres of the laterally-injured brain, and offer evidence for region-specific, CaN-dependent mechanisms.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Campbell
authors.forename: Brian
authors.initials: B
authors.lastname: Low
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kurz
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Patel
authors.forename: Matt T
authors.initials: MT
authors.lastname: Young
authors.forename: Severn B
authors.initials: SB
authors.lastname: Churn
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D019703:Calcineurin / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D019703:Calcineurin