Fingolimod (FTY720) is not protective in the subacute MPTP mouse model of Parkinson's disease and does not lead to a sustainable increase of brain ‐derived neurotrophic factor

Fingolimod is an approved oral drug for multiple sclerosis. Its systemic adminstration increases brain ‐derived neurotrophic factor in the brain (a, left). We tested whether fingolimod has beneficial effects in the MPTP mouse model of Parkinson's disease. Repeated administration of fingolimod in different dosing regimens did not alter the degeneration of dopaminergic neurons or dopaminergic axon te rminals (b). This result differs from previous findings in other models of Parkinson's disease. It can be explained by the fact that repeated administration of fingolimod did not lead to a sustained rise in brain‐derived neurotrophic factor (a, right). AbstractParkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons and aggregates of α‐synuclein termed Lewy bodies. Fingolimod (FTY720) is an agonist of sphingosine‐1 phosphate receptors and an approved oral treatment for multiple sclerosis. Fingolimod elevates brain‐derived neurotrophic factor (BDNF), an important neurotrophic factor for dopaminergic neurons. BDNF and fingo limod are beneficial in several animal models of PD. In order to validate the therapeutic potential of fingolimod for the treatment of PD, we tested its effect in the subacute MPTP mouse model of PD. MPTP or vehicle was applied i.p. in doses of 30 mg/kg MPTP on five consecutive days. In order to re capitulate the combination of dopamine loss and α‐synuclein aggregates found in PD, MPTP was first administered in Thy1‐A...
Source: Journal of Neurochemistry - Category: Neurology Authors: Tags: Original Article Source Type: research