Increase of monoamine oxidase-B activity in the brain of scrapie-infected hamsters.
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.
Adjou
Karim Tarik
KT
Laboratoire de Pathologie du Bétail et des Animaux de Basse-cour, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort Cedex, France. kadjou@vet-alfort.fr
Dilda
Pierre
P
Aumond
Pascal
P
Gueddari
Salah
S
Deslys
Jean-Philippe
JP
Dormont
Dominique
D
Seman
Michel
M
D000666:Amphotericin B / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008647:Mesocricetus; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009410:Nerve Degeneration / Q000201:enzymology / Q000503:physiopathology; D018620:PrPSc Proteins / Q000378:metabolism*; D012608:Scrapie / Q000201:enzymology* / Q000503:physiopathology
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D018620:PrPSc Proteins; C074660:MS 8209; D000666:Amphotericin B; D008995:Monoamine Oxidase