Comparative effects of FK-506, rapamycin and cyclosporin A, on the in vitro differentiation of dorsal root ganglia explants and septal cholinergic neurons.
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 explants. 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 (-78% at 1 nM in thoracic DRG). 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.
Carreau
A
A
Synthélabo Recherche, CNS Research Department, Bagneux, France.
Gueugnon
J
J
Benavides
J
J
Vigé
X
X
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009924:Organ Culture Techniques; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus