Mechanisms of dendritic spine remodeling in a rat model of traumatic brain injury

• Published in: Journal of neurotrauma Vol. 29; no. 2; pp. 218 - 234
• Main Authors: Campbell, John N, Low, Brian, Kurz, Jonathan E, Patel, Sagar S, Young, Matt T, Churn, Severn B
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 20.01.2012
• Subjects: Animals; Brain damage; Brain Injuries - drug therapy; Brain Injuries - pathology; Brain Injuries - physiopathology; Calcineurin - metabolism; Dendritic Spines - drug effects; Dendritic Spines - pathology; Disease Models, Animal; Enzymes; Male; Nerve Degeneration - drug therapy; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Original; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Synaptic Transmission - physiology
• ISSN: 0897-7151; 1557-9042
• DOI: 10.1089/neu.2011.1762

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.