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In SCD, haemoglobin polymerization causes red blood cells to assume a rigid sickle\u2010shape leading to neurovascular alterations, including development of vascular dementia \u2013 characterized by cognitive impairment and reduced cerebral perfusion. Although SCD affects both sexes, sex\u2010specific differences remain unclear. Here, we investigated the mechanisms underlying vascular dementia in female and male Townes mice (a model of SCD), with focus on the role of protein arginine methyltransferases (PRMTs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Middle\u2010aged female and male Townes and C57BL\/6J mice were assessed for functional outcomes (open field, Y\u2010maze and novel object recognition test) and neurovascular alterations. Cortex and hippocampus were collected for protein quantification and nitric oxide (NO) metabolite analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Middle\u2010aged Townes mice exhibited (1) sex\u2010dependent dysregulation of Type I PRMTs, with females showing increased and males decreased levels; (2) altered levels of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase 1 and 2, with females elevated and males reduced; (3) increased endothelial NO synthase, decreased inducible NO synthase and metabolites; (4) neurovascular coupling dysfunction; (5) blood\u2013brain barrier leakage and decreased tight junction proteins; and (6) reduced mobility, increased anxiety\u2010like behaviour and impaired memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Female Townes mice exhibit greater molecular, vascular and behavioural abnormalities than males. These findings suggest that dysregulated NO signalling by Type I PRMTs contributes to vascular deficits and cognitive dysfunction, highlighting the role of PRMTs and the NO pathway in neurovascular and behavioural phenotypes associated with SCD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70535","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:01:26Z","timestamp":1783058486000},"page":"5586-5601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of protein arginine methyltransferases in sickle cell\u2010mediated neurovascular impairments in mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Julia","family":"Zaccarelli\u2010Magalh\u00e3es","sequence":"first","affiliation":[{"name":"Department of Neurology, McGovern Medical School University of Texas Health Science Center  Houston Texas 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