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The mTOR pathway also regulates angiogenesis. For the present study, therefore, we queried whether loss of<jats:italic>Pten<\/jats:italic>or<jats:italic>Tsc2<\/jats:italic>, both mTOR negative regulators, alters brain vasculature in three mouse models: one with<jats:italic>Pten<\/jats:italic>loss restricted to hippocampal dentate granule cells [DGC-<jats:italic>Pten<\/jats:italic>knock-outs (KOs)], a second with widespread<jats:italic>Pten<\/jats:italic>loss from excitatory forebrain neurons (FB-<jats:italic>Pten<\/jats:italic>KOs) and a third with focal loss of<jats:italic>Tsc2<\/jats:italic>from cortical excitatory neurons (f-<jats:italic>Tsc2<\/jats:italic>KOs). Total hippocampal vessel length and volume per dentate gyrus were dramatically increased in DGC-<jats:italic>Pten<\/jats:italic>knock-outs. DGC-<jats:italic>Pten<\/jats:italic>knock-outs had larger dentate gyri overall, however, and when normalized to these larger structures, vessel density was preserved. In addition, tests of blood-brain barrier integrity did not reveal increased permeability. FB-<jats:italic>Pten<\/jats:italic>KOs recapitulated the findings in the more restricted DGC-<jats:italic>Pten<\/jats:italic>KOs, with increased vessel area, but preserved vessel density. FB-<jats:italic>Pten<\/jats:italic>KOs did, however, exhibit elevated levels of the angiogenic factor VegfA. In contrast to findings with<jats:italic>Pten<\/jats:italic>, focal loss of<jats:italic>Tsc2<\/jats:italic>from cortical excitatory neurons produced a localized increase in vessel density. Together, these studies demonstrate that hypervascularization is not a consistent feature of mTOR hyperactivation models and suggest that loss of different mTOR pathway regulatory genes exert distinct effects on angiogenesis.<\/jats:p>","DOI":"10.1523\/eneuro.0340-22.2023","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T18:50:30Z","timestamp":1675968630000},"page":"ENEURO.0340-22.2023","source":"Crossref","is-referenced-by-count":13,"title":["Neurovascular Development in<i>Pten<\/i>and<i>Tsc2<\/i>Mouse Mutants"],"prefix":"10.1523","volume":"10","author":[{"given":"Mary","family":"Dusing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candi L.","family":"LaSarge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian 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