Comparative effects of FK-506, rapamycin and cyclosporin A, on the in vitro differentiation of dorsal root ganglia explants and septal cholinergic neurons

Abstract There is increasing evidence that immunophilins play a role in neural development and differentiation. We have studied the neurotrophic effects of FK-506, rapamycin and cyclosporin A (CsA) on dorsal root ganglia (DRG) taken from different segmental levels (cervical, thoracic and lumbar/sacral), and on rat embryonic septal cholinergic neurons in culture. At a low concentration (1 nM), FK-506 significantly increased (+ 83%) the number of neurites of thoracic DRG expiants. At a higher concentration (100 nM), it also enhanced the neuritogenesis of thoracic (+ 100%) and lumbar/sacral (+ 57%) DRG, but not cervical DRG explants. Rapamycin displayed a converse effect, reducing the development of DRG explants from cervical and thoracic segments. CsA (from 1 to 100 nM) was without effect on DRG neuritogenesis. In contrast to nerve growth factor (NGF), which increased neurite length (+ 116% at 3 ng/ml), neither FK-506 nor rapamycin affected this parameter.