E. Koutsilieri et al., SELEGILINE IS NEUROPROTECTIVE IN PRIMARY BRAIN CULTURES TREATED WITH 1-METHYL-4-PHENYLPYRIDINIUM, European journal of pharmacology, 306(1-3), 1996, pp. 181-186
The ability of selegiline to protect against the neurotoxin 1-methyl-4
-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the i
nhibition of the conversion of MPTP to 1-methyl-4-phenylpyridinium (MP
P(+)), catalyzed by monoamine oxidase-B. Selegiline, however, has been
found to rescue neurons in MPP(+)-treated mice after they have sustai
ned lethal damage independently of monoamine oxidase-B inhibition. In
our present study, we investigate whether selegiline can protect and/o
r rescue MPP(+)-injured dopaminergic neurons in co-cultures of mesence
phalic and striatal cells of embryonic C57B1/6 mouse brains. Cells wer
e exposed to selegiline (1, 10, 100 mu M) in three different schemes:
(i) in control cultures on the 8th day for 48 h; (ii) pretreatment: on
the 8th day for 48 h, followed by administration of MPP(+) (0.5 mu M)
on the 9th day for 24 h; (iii) delayed treatment: on the 9th day for
48 h, while MPP(+) was administered on the 8th day and remained in cul
ture during treatment with selegiline. In the delayed scheme, selegili
ne (1 mu M) increased dopamine content, number of tyrosine hydroxylase
immunoreactive cells and astrocytes in the cultures. We question whet
her selegiline protects cells injured by a toxic stressor via an astro
cyte-mediated mechanism.