UNASSIGNED: @entity1092 ( @entity3262 ) is a neurotherapeutic drug prescribed for @entity410 , @entity162 and @entity2704 , including @entity1 of reproductive age. @entity3262 is a well-known teratogen that produces @entity600 in many organs including the nervous system, as well as @entity245 , including @entity1032 and @entity2438 . In developing brain, few studies have examined @entity3262 effects on glial cells, particularly astrocytes. To investigate effects on primary glial precursors, we developed new cell culture and in vivo models using frontal cerebral cortex of postnatal day (P2) @entity35 . In vitro, @entity3262 exposure elicited dose-dependent, biphasic effects on DNA synthesis and proliferation. In vivo @entity3262 (300 mg/kg) exposure from P2 to P4 increased both DNA synthesis and cell proliferation, affecting primarily astrocyte precursors, as >75% of mitotic cells expressed brain lipid-binding protein. Significantly, the consequence of early @entity3262 exposure was increased astrocytes, as both @entity21078 + cells and glial fibrillary acidic protein were increased in adolescent brain. Molecularly, @entity3262 served as an HDAC inhibitor in vitro and in vivo, as enhanced proliferation was accompanied by increased histone acetylation whereas it elicited changes in culture in cell-cycle regulators, including @entity68959 , and cyclin-dependent kinase (CDK) inhibitors, @entity7504 and @entity5447 . Collectively, these data suggest clinically relevant @entity3262 exposures stimulate glial precursor proliferation, though at higher doses can elicit inhibition through differential regulation of CDK inhibitors. Because changes in glial cell functions are proposed as mechanisms contributing to @entity146 , these observations suggest @entity3262 teratogenic actions may be mediated through changes in astrocyte generation during development. This article is protected by copyright. All rights reserved.

@entity1092 stimulates proliferation of glial precursors during cortical gliogenesis in developing XXXX .

@entity1 :: ('9606', 'Species') :: ['women'] @entity5447 :: ('83571(Tax:10116)', 'Gene') :: ['p27'] @entity162 :: ('MESH:D001714', 'Disease') :: ['bipolar disorder'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizures'] @entity1032 :: ('MESH:D008607', 'Disease') :: ['mental retardation'] @entity21078 :: ('25742(Tax:10116)', 'Gene') :: ['S100-b'] @entity7504 :: ('24525(Tax:10116)', 'Gene') :: ['p21'] @entity3262 :: ('D014635', 'Chemical') :: ['VPA'] @entity146 :: ('MESH:D001523', 'Disease') :: ['neuropsychiatric disorders'] @entity1092 :: ('MESH:D014635', 'Chemical') :: ['Valproic acid'] @entity245 :: ('MESH:D002658', 'Disease') :: ['later neurodevelopmental disorders'] @entity2438 :: ('MESH:D001321', 'Disease') :: ['autism'] @entity600 :: ('MESH:D000014', 'Disease') :: ['congenital malformations'] @entity2704 :: ('MESH:D008881', 'Disease') :: ['migraine'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity68959 :: ('58919;25729', 'Gene') :: ['cyclin D1 and E']
@entity35 :: (10116,Species) :: ['rat']
