Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes.
We investigated the effects of selegiline and desmethylselegiline on synthesis of neurotrophic factors in cultured mouse astrocytes. Treatment with 2 mM selegiline for 24 h increased the contents of NGF, BDNF, and GDNF in the culture medium 26-, 1.7-, and 4.2-fold over the control, respectively. With this drug the maximum relative mRNA levels of NGF, BDNF, and GDNF were 6.2-fold at 2 h, 3.4-fold at 6 h, and 2.7-fold at 2 h, respectively. Selegiline at 0.2 mM completely inhibited the MAO activity, but had no effect on the content of neurotrophic factors, suggesting that stimulation of neurotrophic factors by selegiline is independent of MAO-B inhibition. Desmethylselegiline at 1.68 mM for 24 h elevated the NGF, BDNF, and GDNF contents 4.1-, 1.7-, and 2.4-fold over the control, respectively; and the relative transcript levels of NGF, BDNF, and GDNF reached 2.6-fold at 2 h, 1.7-fold at 6 h, and 1.8-fold at 2 h, respectively. These findings suggest that selegiline and desmethylselegiline may protect neurons by up-regulating endogenous NGF, BDNF, and GDNF synthesis.
Mizuta
I
I
Clinical Research Center, Utano National Hospital, Narutaki, Ukyo-ku, Kyoto, 616-8255, Japan.
Ohta
M
M
Ohta
K
K
Nishimura
M
M
Mizuta
E
E
Hayashi
K
K
Kuno
S
S
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002478:Cells, Cultured; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051379:Mice; D008813:Mice, Inbred ICR; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D012642:Selegiline / Q000494:pharmacology*
D000662:Amphetamines; D019208:Brain-Derived Neurotrophic Factor; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008996:Monoamine Oxidase Inhibitors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012642:Selegiline; C017861:desmethylselegiline; D020932:Nerve Growth Factor