In the present study, the purpose is to determine activities of monoamine
oxidases (
MAO) in the brain of 263K
scrapie-infected hamsters during the development of this experimental
prion disease. Indeed,
MAO activity modifications which have already been related in aging and neurodegenerations is suspected to be involved in the neuron loss process by elevated
hydrogen peroxide formation.
Monoamine oxidase type A (
MAO-A) and B (
MAO-B) activities were followed in the brain at different stages of the disease.
MAO-A activity did not change significantly during the evolution of the disease. However, concerning the
MAO-B activity, a significant increase was observed from 50 days post-
infection and through the course of the disease and reached 42.9+/-5.3% at its ultimate stage. Regarding these results,
MAO-B could be a potential therapeutic target then we have performed a pre-clinical treatment with irreversible (
Selegiline or
L-deprenyl) or and reversible (MS-9510)
MAO-B inhibitors used alone or in association with an anti-
scrapie drug such as
MS-8209, an
amphotericin B derivative. Our results show that none of the
MAO-B inhibitors used was able to delay the onset of the disease. Neither these
MAO-B inhibitors nor R-
NMDA inhibitors (MK-801) can enhance the effects of
MS-8209. The present findings clearly indicate a significant increase of cerebral
MAO-B activity in
scrapie-infected hamsters. Furthermore, inhibitors of
MAO-B do not have any curative or palliative effect on this experimental model indicating that the raise of this activity is probably more a consequence rather than a causal event of the neurodegenerative process.