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PPAR\u03b1 agonists partially dampen this neuroinflammation in some models of brain insult, but neuronal loss was not the triggering cause in any of them. This study examines the anti-inflammatory and immunomodulatory properties of the PPAR\u03b1 agonist oleoylethanolamide (OEA) in the Purkinje Cell Degeneration (PCD) mouse, which exhibits striking neuroinflammation caused by aggressive loss of cerebellar Purkinje neurons. Using real-time quantitative polymerase chain reaction and immunostaining, we quantified changes in pro- and anti-inflammatory markers, microglial density and marker-based phenotype, and overall leukocyte recruitment at different time points after OEA administration. OEA was found to modulate cerebellar neuroinflammation by increasing the gene expression of proinflammatory mediators at the onset of neurodegeneration and decreasing it over time. OEA also enhanced the expression of anti-inflammatory and neuroprotective factors and the Ppar\u03b1 gene. Regarding microgliosis, OEA reduced microglial density\u2014especially in regions where it is preferentially located in PCD mice\u2014and shifted the microglial phenotype towards an anti-inflammatory state. Finally, OEA prevented massive leukocyte infiltration into the cerebellum. Overall, our findings suggest that OEA may change the environment to protect neurons from degeneration caused by exacerbated inflammation.<\/jats:p>","DOI":"10.3390\/ijms24119691","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T10:08:41Z","timestamp":1685700521000},"page":"9691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8953-9018","authenticated-orcid":false,"given":"Ester","family":"P\u00e9rez-Mart\u00edn","sequence":"first","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-8220","authenticated-orcid":false,"given":"Laura","family":"P\u00e9rez-Revuelta","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0743-383X","authenticated-orcid":false,"given":"Cristina","family":"Barahona-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-3270","authenticated-orcid":false,"given":"David","family":"P\u00e9rez-Boyero","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-7616","authenticated-orcid":false,"given":"Jos\u00e9 R.","family":"Alonso","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3705-817X","authenticated-orcid":false,"given":"David","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-5506","authenticated-orcid":false,"given":"Eduardo","family":"Weruaga","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute of Neuroscience of Castile and Leon (INCyL), Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/s41590-018-0212-1","article-title":"The Identity and Function of Microglia in Neurodegeneration","volume":"19","author":"Song","year":"2018","journal-title":"Nat. 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