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These are characterized by an upregulation of interleukin (IL)\u20104 levels. Allergies share a strong comorbidity with Autism Spectrum Disorders (ASD) and Attention\u2010Deficit\/Hyperactivity Disorder (ADHD). We previously showed that early\u2010life allergic asthma induces hyperactive and impulsive behaviors in mice. This phenotype was reproduced in animals administered with IL\u20104 in the second postnatal week. Mechanistically, elevated IL\u20104 levels prevented microglia\u2010mediated engulfment of neurons in the cerebellum, resulting in a surplus of granule cells and consequent dysfunction in cerebellar connectivity. Here, we aimed to further understand the impact of early IL\u20104 administration in microglia of the cerebellum and the prefrontal cortex (PFC), two brain regions with protracted developmental programs and susceptible to immune system malfunction after birth. While IL\u20104 administration induced differential short\u2010term effects on microglia in the cerebellum and PFC, both regions presented similar microglial features in adult mice. Although Sholl analysis did not reveal significant alterations in overall microglia morphology at postnatal day (P)10, the density of microglia was decreased in the cerebellum at this age, especially in the granular layer (GL), but remained unaltered in the PFC. Interestingly, the presence of microglia with phagocytic cups, morphological features important for whole\u2010cell engulfment, was decreased in both regions. When assessing the long\u2010term consequences of IL\u20104 administration, cerebellar and PFC microglia were hypo\u2010ramified and exhibited increased overall density. Importantly, microglia alterations were exclusive to the GL of the cerebellum and the infralimbic region of the PFC. Our results show that postnatal elevated levels of IL\u20104 impair the percentage of microglia engaged in cell clearing in two brain regions with protracted developmental programs. Interestingly, IL\u20104\u2010exposed microglia adapt a similar phenotype in the adult cerebellum and PFC. Our data suggest that this early\u2010life increase in IL\u20104 levels is sufficient to elicit long\u2010lasting alterations in microglia, potentially increasing cell susceptibility to later insults.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16266-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16266","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:14:11Z","timestamp":1734326051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Early\u2010life\n                    <scp>IL<\/scp>\n                    \u20104 administration induces long\u2010term changes in microglia in the cerebellum and prefrontal cortex"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-0384","authenticated-orcid":false,"given":"Pedro A.","family":"Ferreira","sequence":"first","affiliation":[{"name":"CNC\u2010UC\u2014Center for Neuroscience and Cell Biology University of Coimbra  Coimbra Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology University of Coimbra  Coimbra Portugal"},{"name":"Doctoral Programme in Biosciences, Department of Life Sciences University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Lebre","sequence":"additional","affiliation":[{"name":"CNC\u2010UC\u2014Center for Neuroscience and Cell Biology University of Coimbra  Coimbra Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology University of 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