Fingolimod induces neurogenesis in adult mouse hippocampus and improves contextual fear memory

Translational Psychiatry
P EfstathopoulosI Charalampopoulos

Abstract

Fingolimod (FTY720) was the first per os administered disease-modifying agent approved for the treatment of relapsing-remitting multiple sclerosis. It is thought that fingolimod modulates the immune response by activating sphingosine-1 phosphate receptor type 1 (S1P1) on lymphocytes following its in vivo phosphorylation. In addition to its immune-related effects, there is evidence that fingolimod exerts several other effects in the central nervous system, including regulation of the proliferation, survival and differentiation of various cell types and their precursors. In the present study, we have investigated the effect of fingolimod on the production of new neurons in the adult mouse hippocampus and the association of this effect with the ability for pattern separation, an established adult neurogenesis-dependent memory function. Immunofluorescence analysis after chronic administration of a physiologic dose of fingolimod (0.3 mg kg(-1)) revealed a significant increase in both the proliferation and the survival of neural progenitors in the area of dentate gyrus of hippocampus, compared with control animals. These effects were replicated in vitro, in cultures of murine hippocampal neural stem/precursor cells that express S1P1 ...Continue Reading

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Apr 2, 2017·Journal of Pharmacological Sciences·Ismael Segura-UlateRuth G Perez
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Aug 28, 2021·Pharmacology & Therapeutics·Emanuela Colombo, Cinthia Farina

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
histone acetylation

Software Mentioned

power
Watcher
Excel
Graphpad Prism

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