Fingolimod Modulates Dendritic Architecture in a BDNF-Dependent Manner.
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Authors
Patnaik, AbhisarikaSpiombi, Eleonora
Frasca, Angelisa
Landsberger, Nicoletta
Zagrebelsky, Marta
Korte, Martin
Issue Date
2020-04-27Submitted date
2020-03-30
Metadata
Show full item recordAbstract
The brain-derived neurotrophic factor (BDNF) plays crucial roles in both the developing and mature brain. Moreover, alterations in BDNF levels are correlated with the cognitive impairment observed in several neurological diseases. Among the different therapeutic strategies developed to improve endogenous BDNF levels is the administration of the BDNF-inducing drug Fingolimod, an agonist of the sphingosine-1-phosphate receptor. Fingolimod treatment was shown to rescue diverse symptoms associated with several neurological conditions (i.e., Alzheimer disease, Rett syndrome). However, the cellular mechanisms through which Fingolimod mediates its BDNF-dependent therapeutic effects remain unclear. We show that Fingolimod regulates the dendritic architecture, dendritic spine density and morphology of healthy mature primary hippocampal neurons. Moreover, the application of Fingolimod upregulates the expression of activity-related proteins c-Fos and pERK1/2 in these cells. Importantly, we show that BDNF release is required for these actions of Fingolimod. As alterations in neuronal structure underlie cognitive impairment, we tested whether Fingolimod application might prevent the abnormalities in neuronal structure typical of two neurodevelopmental disorders, namely Rett syndrome and Cdk5 deficiency disorder. We found a significant rescue in the neurite architecture of developing cortical neurons from Mecp2 and Cdkl5 mutant mice. Our study provides insights into understanding the BDNF-dependent therapeutic actions of Fingolimod.Publisher
MDPIPubMed ID
32349283Type
ArticleLanguage
enEISSN
1422-0067ae974a485f413a2113503eed53cd6c53
10.3390/ijms21093079
Scopus Count
The following license files are associated with this item:
- Creative Commons