Only 14 pages are availabe for public view
Nitropropionic acid (3-NP), a mitochondrial toxin, is considered a
reliable agent for inducing HD-like phenotype in experimental animals.
Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor
hypoactivity, increased oxidative stress, activation of apoptotic cascade and
bilateral striatal lesions are the major manifestations of 3-NP-induced
neurotoxicity. Selegiline is a non-competitive monoamine oxidase-B (MAO-B)
inhibitor with previously reported antioxidant and antiapoptotic effects. The
present study was designed to investigate neuroprotective effect of selegiline
on 3-NP induced neurotoxicity. Rats administered 3-NP (20 mg/kg, i.p.) for
four consecutive days exhibited PPI deficits, locomotor hypoactivity, increased
striatal and cortical malondialdehyde (MDA) and reduced respective
glutathione (GSH) level, catalase and superoxide dismutase (SOD) activities.
Changes in the level of apoptotic regulatory gene expressions were
demonstrated as increased striatal and cortical caspase-3 and Bax expression
and decreased respective Bcl2 expression. Selegiline was given by i.p. injection
at doses 2.5, 5 and10 mg/kg, 3 days prior to- and continued daily, 30 minutes
before 3-NP administration. The high dose levels of selegiline (5 and 10
mg/kg), significantly increased locomotor activity, improved PPI, reduced
striatal and cortical MDA, caspase-3 and Bax and increased respective GSH
level, catalase and superoxide dismutase activities and Bcl2 expression.
Selegiline at dose 2.5 mg/kg could only reverse some of the manifestations of
3-NP-induced neurotoxicity. It could significantly improve PPI, reduce striatal
MDA level and Bax expression, and increase striatal GSH level, catalase and
superoxide dismutase activities. It could also significantly increase cortical
superoxide dismutase level and decreased cortical Bax expression. Histological
examination further affirmed the neuroprotective effect of high dose levels of
selegiline against 3-NP toxicity. Taken together, these results suggest that
selegiline attenuate 3-NP-induced neurotoxicity. This neuroprotective effect
may be related to antioxidant properties and antiapoptotic effects.
Key words: 3-nitropropionic acid; Selegiline; Prepulse inhibition; Glutathione;