Fingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer’s disease

Fingolimod is a functional sphingosine 1-phosphate (S1P) receptor antagonist that has been approved for the treatment for MS (Multiple Sclerosis). It has been shown that the anti-inflammatory effect of fingolimod is mediated through S1P1 receptors on lymphocytes, preventing the migration of these cells from peripheral lymphoid organs into the CNS, suggesting it may protect against neuroinflammation. Fingolimod can cross the blood–brain-barrier (BBB) therefore showing a potential effect on CNS cells including neurons, astrocytes, microglia, and oligodendrocytes expressing S1P receptors. Recently, it has been reported that treatment with fingolimod is associated with microglial neuroprotective effects, including reduction of pro-inflammatory cytokines and increased levels of brain-derived neurotrophic factor (BDNF).  At least one recent study has suggested direct effects of the drugs on neurons. However, it remains unclear whether modulation of BDNF by the drug in vivo is a direct or indirect effect, and what cell types are involved. This study was designed to test the effect of fingolimod on amyloid β pathology and neuroinflammation associated with activation of microglia and astrocytes in a mouse model of AD.