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Here, we present the systematic analysis of regional CB\n                      <jats:sub>1<\/jats:sub>\n                      R expression in the developing human brain from gestational week 14 until birth. In parallel, we diagrammed differences in CB\n                      <jats:sub>1<\/jats:sub>\n                      R development in Down syndrome foetuses and identified altered CB\n                      <jats:sub>1<\/jats:sub>\n                      R signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Foetal brains with normal development or with Down's syndrome were analysed using standard immunohistochemistry, digitalised light microscopy and image analysis (NanoZoomer). CB\n                      <jats:sub>1<\/jats:sub>\n                      R function was investigated by in vitro neuropharmacology from neonatal Ts65Dn transgenic mice brains carrying an additional copy of ~90 conserved protein\u2010coding gene orthologues of the human chromosome 21.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We detected a meshwork of fine\u2010calibre, often varicose processes between the subventricular and intermediate zones of the cortical plate in the late first trimester, when telencephalic fibre tracts develop. The density of CB\n                      <jats:sub>1<\/jats:sub>\n                      Rs gradually decreased during the second and third trimesters in the neocortex. In contrast, CB\n                      <jats:sub>1<\/jats:sub>\n                      R density was maintained, or even increased, in the hippocampus. We found the onset of CB\n                      <jats:sub>1<\/jats:sub>\n                      R expression being delayed by \u22651\u00a0month in age\u2010matched foetal brains with Down's syndrome. In vitro, CB\n                      <jats:sub>1<\/jats:sub>\n                      R excitation induced excess microtubule stabilisation and, consequently, reduced neurite outgrowth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We suggest that neuroarchitectural impairments in Down's syndrome brains involve the delayed development and errant functions of the endocannabinoid system, with a particular impact on endocannabinoids modulating axonal wiring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12887","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T18:55:20Z","timestamp":1675104920000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Regional redistribution of CB1 cannabinoid receptors in human foetal brains with Down's syndrome and their functional modifications in Ts65Dn\n                    <sup>+\/+<\/sup>\n                    mice"],"prefix":"10.1111","volume":"49","author":[{"given":"\u00c1goston","family":"Patthy","sequence":"first","affiliation":[{"name":"Department of Anatomy Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Hanics","sequence":"additional","affiliation":[{"name":"Department of Anatomy Semmelweis University  Budapest Hungary"},{"name":"SE NAP Research Group of Experimental Neuroanatomy and Developmental Biology Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gergely","family":"Zachar","sequence":"additional","affiliation":[{"name":"Department of Anatomy Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"G\u00e1bor 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