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Valproic acid alters the expression of HIF‐1α in embryonic brains in a valproic acid rodent model of autism
Author(s) -
Oman Jordan,
Ubah Dominic,
Rivas Diana,
Triyasakorn Korawin,
Bhushan Alok,
Lai James,
Awale Prabha
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03260
Subject(s) - valproic acid , rodent , embryonic stem cell , rodent model , neuroscience , autism , chemistry , biology , psychology , medicine , epilepsy , developmental psychology , biochemistry , gene , ecology
Although studies have investigated the role of Valproic acid (VPA) in impaired neurogenesis in rodent models of autism, the molecular mechanisms that underlie neural developmental changes during embryonic brain development in this model are poorly understood. Here, we employed a VPA rat model of autism to investigate the effects of VPA treatment on key enzymes of glucose oxidative metabolism namely lactate dehydrogenase (LDH), and genes of the adaptive responses including hypoxia induced factor 1 alpha (HIF‐1α) in embryonic rat brain. Pregnant Wistar rats were administered 600 mg/kg of VPA by intraperitoneal injection on day 12.5 of gestation and embryonic (E) day 15, E17, E20 rat brains were assayed for the activity of LDH. E15, E17 and E20 male and female rat models of VPA‐induced autism showed significantly increased whole brain activities of LDH compared to the corresponding values in control rats. In addition, valproic acid altered the expression of HIF‐1α at the different embryonic time points. Our results suggest at least some of the mechanism underlying impaired neurogenesis in the VPA model maybe partly due to changes in activity of LDH and alteration of HIF‐1α. The altered expression of HIF‐1α regulates the expression of several enzymes and growth factors that may have pathophysiological/pathogenic implications in autism and may ultimately lead to the discovery of new therapeutic target(s) for autism.