Regional calcineurin subunit B isoform expression in rat hippocampus following a traumatic brain injury.
Calcineurin subunit isoforms are implicated in long term potentiation, long term depression, and structural plasticity. Calcineurin inhibitors benefit axonal damage, cellular dysfunction, and cognitive outcomes in animal models of traumatic brain injury (TBI). Distribution of the catalytic calcineurin A subunit is altered and calcineurin activity increased following fluid percussion injury. Alterations in calcineurin subunit A isoform distribution within the hippocampus also occur post controlled cortical impact (CCI) demonstrating a reduction in catalytic subunit distribution in CA1-2 dendritic fields. Furthermore the effect of TBI on the regulatory subunit, calcineurin B, is unknown. Understanding the role of both subunits is necessary to effectively target alterations in calcineurin signaling as current calcineurin inhibitors, such as cyclosporin A and FK-506, rely upon binding sites on both subunits for complete inhibition. The effect of moderate CCI on the expression and distribution of calcineurin B isoforms within the hippocampus was examined at 2h and 2weeks post injury. Calcineurin B isoforms showed increased expression throughout the CA1 and CA2 while there was a decrease in expression within the ipsilateral dentate gyrus. Alterations in CnB isoform expression within the CA1, CA1-2, and dentate gyrus have significant implications for persistent hippocampal dysfunction following TBI. Regional changes in regulatory subunit expression may alter the effect of calcineurin inhibitors regionally following a traumatic brain injury.
Bales
James W
JW
Brain Trauma Research Center, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Ma
Xiecheng
X
Yan
Hong Q
HQ
Jenkins
Larry W
LW
Dixon
C Edward
CE
D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D019703:Calcineurin / Q000378:metabolism*; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013997:Time Factors
D019703:Calcineurin