Expression of Protein Phosphatase 2B (Calcineurin) Subunit A Isoforms in Rat Hippocampus after Traumatic Brain Injury

Calcineurin (CaN) is a calcium/calmodulin-dependent phosphatase directly activated by calcium as a result of neuronal activation that is important for neuronal function. CaN subunit isoforms are implicated in long-term potentiation (LTP), long-term depression (LTD), and structural plasticity. CaN inhibitors are also beneficial to cognitive outcomes in animal models of traumatic brain injury (TBI). There are known changes in the CaN A (CnA) subunit following fluid percussion injury (FPI). The CnA subunit has two isoforms: CnA alpha and CnA beta. The effect of moderate controlled cortical impact (CCI) on distribution of CnA isoforms was examined at 2 h and 2 weeks post-injury. CnA distribution was assayed by immunohistochemistry and graded for non-parametric analysis. Acutely CnA isoforms showed reduced immunoreactivity in stratum radiatum processes of the ipsilateral CA1 and CA1-2. There was also a significant alteration in the immunoreactivity of both CnA isoforms in the ipsilateral dentate gyrus, predominantly within the hidden blade. Alterations in CnA isoform regional distribution within the CA1, CA1-2, and dentate gyrus may have significant implications for persistent hippocampal dysfunction following TBI, including dysfunction in hippocampal plasticity. Understanding alterations in CnA isoform distribution may help improve the targeting of current therapeutic interventions and/or the development of new treatments for TBI.