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Updated: Jul 5, 2026
A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Increase of monoamine oxidase-B activity in the brain of scrapie-infected hamsters
Karim Tarik Adjou1, Pierre Dilda, Pascal Aumond
1Laboratoire de Pathologie du Bétail et des Animaux de Basse-cour, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort Cedex, France. kadjou@vet-alfort.fr
Abstract:
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.
Insights
Monoamine oxidase B (MAO-B) activity significantly increases in the brains of hamsters with experimental prion disease. However, MAO-B inhibitors did not treat or prevent scrapie, suggesting increased MAO-B is a consequence, not a cause, of neurodegeneration.
Area of Science:
- Neuroscience
- Biochemistry
- Prion Disease Research
Background:
- Monoamine oxidases (MAO) are implicated in neurodegenerative diseases.
- MAO activity may contribute to neuronal loss via hydrogen peroxide production.
- Scrapie is an experimental prion disease model for neurodegeneration.
Purpose of the Study:
- To investigate changes in monoamine oxidase A (MAO-A) and B (MAO-B) activity in the brain during experimental scrapie.
- To evaluate the therapeutic potential of MAO-B inhibitors in scrapie-infected hamsters.
Main Methods:
- Assessed MAO-A and MAO-B activities in hamster brains at various stages of 263K scrapie infection.
- Administered MAO-B inhibitors (Selegiline, L-deprenyl, MS-9510) and an anti-scrapie drug (MS-8209) in pre-clinical trials.
- Evaluated the effects of treatments on disease onset and progression.
Main Results:
- MAO-A activity remained unchanged throughout scrapie development.
- MAO-B activity significantly increased from 50 days post-infection, reaching a 42.9% rise at the terminal stage.
- MAO-B inhibitors, alone or with MS-8209, failed to delay disease onset or progression.
- NMDA receptor antagonists did not enhance MS-8209 efficacy.
Conclusions:
- Cerebral MAO-B activity is significantly elevated in scrapie-infected hamsters.
- The increased MAO-B activity appears to be a consequence, not a cause, of the neurodegenerative process in this model.
- MAO-B inhibition is not a viable therapeutic strategy for experimental scrapie.
