Elsevier

Neuroscience Letters

Volume 487, Issue 3, 10 January 2011, Pages 260-263
Neuroscience Letters

Calcineurin inhibition with systemic FK506 treatment increases dendritic branching and dendritic spine density in healthy adult mouse brain

https://doi.org/10.1016/j.neulet.2010.10.033Get rights and content

Abstract

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.

Research highlights

▶ FK506 increases basal dendritic spine density on layer II–III pyramidal neurons. ▶ FK506 increases branching of basal dendritic tree of layer II–III pyramidal neurons. ▶ Calcineurin inhibition changes branching and spine density in healthy adult brain.

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Acknowledgements

This work was supported by NIH grants K99 AG033670-01A1, P50 AG005134, AG08487, and the Alzheimer's Disease Drug Discovery Foundation/Association for Frontotemporal Dementias.

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