Calcineurin inhibition with systemic FK506 treatment increases dendritic branching and dendritic spine density in healthy adult mouse brain.
Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and recent data suggest that calcineurin activation mediates some of the neurotoxicity of the Alzheimer related neurotoxin Aβ. Immunosuppression via calcineurin inhibition with the compound FK506 is an important treatment for organ transplant patients. Here we use Golgi impregnation techniques, along with a new survival analysis-based statistical approach for analysis of dendritic complexity, to show that in healthy adult mice one week of treatment with FK506 affects both the branching patterns and dendritic spine density of cortical neurons. These results indicate that calcineurin inhibition leads to readily detectable changes in brain morphology, further implicating calcineurin related pathways in both the function and structure of the adult brain.
Massachusetts General Hospital/Harvard Medical School, MassGeneral Institute for Neurodegenerative Diseases, 114 16th Street, Charlestown, MA 02129, USA.
Tara L
TL
Spires-Jones
Kevin
K
Kay
Roland
R
Matsouka
Anete
A
Rozkalne
Rebecca A
RA
Betensky
Bradley T
BT
Hyman
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure*; D065095:Calcineurin Inhibitors; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D016559:Tacrolimus / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus