Description
Cortistatin exerts a fine-tuning of the glial dynamics and central immune response during neurodegeneration
C.P. Falo1, V. Ferraz-de-Paula1, I. Forte-Lago1, M. Caro1, F. O´Valle2, E. González-Rey1*
1Institute of Parasitology and Biomedicine (IPBLN-CSIC), Granada, Spain; 2Medicine School, University of Granada, Granada, Spain
*Corresponding Author
Multiple sclerosis (MS) is an autoimmune inflammatory pathology that leads to progressive axonal degeneration with no effective therapy. Development of new treatments relies on a better understanding of the factors involved in the peripheral autoimmune response, in the activation and function of resident glial cells, and in the endogenous repair processes. Cortistatin (CST) is an anti-inflammatory neuropeptide distributed in the nervous and immune systems. Our previous work demonstrated the therapeutic and immunomodulatory effect of CST in the experimental autoimmune encephalomyelitis murine model of MS. However, its therapeutic and endogenous role in the dynamics of glial cells and in the neuroinflammation during de-and remyelination is unknown. To investigate the role of CST bypassing the effects of infiltrating peripheral immune cells, we use a cuprizone-induced demyelination mouse model of MS, and analyze the molecular and cellular mechanisms involved in the interactions of the glial niche. We found that treatment with CST protected from demyelination and induces active remyelination, reduced gliosis, and decreased axonal pathology. To note, lack of CST induced an early exacerbated glial immune response. Moreover, endogenous CST seemed to modulate the oligodendrocyte lineage and function, showed by aberrant myelin patterns in CST-deficient mice. Together, these results suggested that CST modulates the glial niche during the de- and remyelination as a normalizing factor by a combined immunomodulatory and neuroprotective function. In addition, CST seems to be a key endogenous factor in the success/failure of these processes. Finally, these results pointed the relevance of knowing factors that participate in the physiological and pathological crosstalk between the nervous and immune systems, as they could be recognized as new therapeutic agents in neurodegenerative diseases with an inflammatory component.
Ann N Y Acad Sci. 2015; 1351:89-98.
J Immunol. 2013; 191(5):2144-54
Funding: Spanish Ministry of Science and Innovation SAF2010-16923; Spanish Ministry of Economy and Competitiveness SAF2014-58354-R