Immunosuppressive (FK506) and non-immunosuppressive (GPI1046) immunophilin ligands activate neurotrophic factors in the mouse brain.
Based on the fact that several recent reports have indicated that non-immunosuppressive immunophilin ligands (IPLs) can activate neurite outgrowth or nerve regeneration, we investigated the neurotrophic factor-activating abilities of IPLs in vivo in order to clarify the molecular basis of neurotrophic-like activity. Both FK506 (an immunosuppressive IPL) and GPI1046 (a non-immunosuppressive IPL) significantly increased glial cell line-derived neurotrophic factor (GDNF) content in the substantia nigra. In addition, FK506 increased striatal brain-derived neurotrophic factor (BDNF) content significantly. Thus, our present results suggest that the molecular basis of IPL-induced neurotrophic-like activity may be dependent on GDNF and/or BDNF activation.
Tanaka
Ken-ichi
K
Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Japan. kntanaka@cc.okayama-u.ac.jp
Fujita
Naoko
N
Ogawa
Norio
N
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020104:Immunophilins / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D011759:Pyrrolidines / Q000494:pharmacology*; D016559:Tacrolimus / Q000494:pharmacology*
C104949:GPI 1046; D007166:Immunosuppressive Agents; D009414:Nerve Growth Factors; D011759:Pyrrolidines; D020104:Immunophilins; D016559:Tacrolimus