000056170 001__ 56170
000056170 005__ 20200221144210.0
000056170 0247_ $$2doi$$a10.1038/srep25663
000056170 0248_ $$2sideral$$a95308
000056170 037__ $$aART-2016-95308
000056170 041__ $$aeng
000056170 100__ $$aMartínez-Muriana, A.
000056170 245__ $$aCSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves
000056170 260__ $$c2016
000056170 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056170 5203_ $$aInflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1G93A transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1G93A mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1G93A mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease.
000056170 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2013-48431-R
000056170 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056170 590__ $$a4.259$$b2016
000056170 591__ $$aMULTIDISCIPLINARY SCIENCES$$b10 / 63 = 0.159$$c2016$$dQ1$$eT1
000056170 592__ $$a1.691$$b2016
000056170 593__ $$aMultidisciplinary$$c2016$$dQ1
000056170 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056170 700__ $$aMancuso, R.
000056170 700__ $$aFrancos-Quijorna, I.
000056170 700__ $$aOlmos-Alonso, A.
000056170 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, R.$$uUniversidad de Zaragoza
000056170 700__ $$aPerry, V.H.
000056170 700__ $$aNavarro, X.
000056170 700__ $$aGomez-Nicola, D.
000056170 700__ $$aLópez-Vales, R.
000056170 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000056170 773__ $$g6 (2016), 25663 [13 pp]$$pSci. rep.$$tSCIENTIFIC REPORTS$$x2045-2322
000056170 8564_ $$s2517219$$uhttps://zaguan.unizar.es/record/56170/files/texto_completo.pdf$$yVersión publicada
000056170 8564_ $$s107162$$uhttps://zaguan.unizar.es/record/56170/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056170 909CO $$ooai:zaguan.unizar.es:56170$$particulos$$pdriver
000056170 951__ $$a2020-02-21-13:10:58
000056170 980__ $$aARTICLE