IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Neuroregenerative and neuroprotective actions of immunophilin ligands in murine models
Autor/es:
DANERI C, PATIÑO M, GALIGNIANA MD
Reunión:
Congreso; LXII Reunión Anual de SAIC; 2017
Resumen:
Immunophilins (IMMs) are a family of intracellular proteins that bind immunosuppressive drugs. They are referred to as FK506-binding proteins (FKBPs) when they bind FK506, and cyclophilins (CyPs) when they bind cyclosporine A (CsA). In previous studies performed in cell cultures, we demonstrated that FK506 shows neuroregenerative and neuroprotective actions via FKBPs, the expression balance between FKBP52 and FKBP51 playing a key role during those processes. In this study, we demonstrated the neurotrophic action in vivo using a murine model, and extended the analysis to CsA since both drugs were able to promote neurite outgrowth in undifferentiated N2a cells. We performed organotypic cultures of prefrontal brain cortex or spinal cord; 250 µm slices were treated with 0.5 mM H2O2 and/or 1µM FK506 or CsA to generate oxidative stress. Drug pretreatment attenuates the induction of HSP70 and HSP90 observed by treatments with H2O2, suggesting a protective action on nervous tissue. Western blots show similar results after frontoparietal cortex injections of mice with CoCl2 to generate a hypoxia-like condition. Importantly, in vivo responses were also greatly favoured by FK506 or CsA treatment. Thus, to evidence locomotor performances, a Rotarod test was assessed with FK506- or CsA-treated mice, showing both a better performance in most evaluated parameters. In order to analyze the locomotor recovery, spinal cord injured mice were injected daily with FK506 or CsA, and a Basso-Mouse Scale test was performed. Locomotor recovery was faster and greater in drug-treated mice than in vehicle-injected controls. Importantly, recovery was better in FKBP51-KO mice since this IMM is an inhibitory protein, whereas recovery was less efficient in FKBP52-KO mice since it is a positive factor. Microscopy studies of tissue for the expression of trophic factors or inflammatory reaction show improvement by treatments with IMM ligands. We conclude that IMMs are novel neurotrophic factors.