early life stress enhancement of limbic epileptogenesis in adult rats mechanistic insights早期生活压力增强边缘epileptogenesis对成年老鼠的机械的见解.pdfVIP

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights 1 1 2 3 1,4,5 Gaurav Kumar , Nigel C. Jones , Margaret J. Morris , Sandra Rees , Terence J. O’Brien , Michael R. Salzberg6,7* 1 Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia, 2 Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia, 3 Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia, 4 Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia, 5 Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia, 6 St. Vincent’s Mental Health Service, St. Vincent’s Hospital, Fitzroy, Australia, 7 Department of Psychiatry, St. Vincent’s Hospital, University of Melbourne, Fitzroy, Australia Abstract Background: Exposure to early postnatal stress is known to hasten the progression of kindling epileptogenesis in adult rats. Despite the significance of this for understanding mesial temporal lobe epilepsy (MTLE) and its associated psychopathology, research findings regarding underlying mechanisms are sparse. Of several possibilities, one important candidate mechanism is early life ‘programming’ of the hypothalamic-pituitary-adrenal (HPA) axis by postnatal stress. Elevated corticosterone (CORT) in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS would augment seizure-related corticosterone (CORT) release and enhance neuroplastic changes in the hippocampus. Methodology/Principal Findings: Eight-