title: Sustained Impairments in Brain Insulin/IGF Signaling in Adolescent Rats Subjected to Binge Alcohol Exposures during Development.
abstract: BACKGROUND
  Chronic or binge ethanol exposures during development can cause fetal alcohol spectrum disorder (FASD) which consists of an array of neurobehavioral deficits, together with structural, molecular, biochemical, and neurotransmitter abnormalities in the brain. Previous studies showed that perinatal neurodevelopmental defects in FASD are associated with inhibition of brain insulin and insulin-like growth factor (IGF) signaling. However, it is not known whether sustained abnormalities in adolescent brain structure and function are mediated by the same phenomena.
  
  
  OBJECTIVE
  Using an early postnatal (3rdtrimester equivalent) binge ethanol exposure model, we assessed neurobehavioral function, structure, and the integrity of insulin/IGF signaling in young adolescent cerebella.
  
  
  METHODS
  Long Evans male rats were treated with 50 µl of saline (vehicle) or 2 mg/kg of ethanol by i.p. injection on postnatal days (P) 2, 4, 6, and 8. On P19-20, rats were subjected to rotarod testing of motor function, and on P30, they were sacrificed to harvest cerebella for histological, molecular, and biochemical studies.
  
  
  RESULTS
  Binge ethanol exposures impaired motor function, caused sustained cerebellar hypocellularity, and reduced neuronal and oligodendrocyte gene expression. These effects were associated with significant deficits in insulin and IGF signaling, including impaired receptor binding, reduced Akt, and increased GSK-3β activation.
  
  
  CONCLUSIONS
  FASD-associated neurobehavioral, structural, and functional abnormalities in young adolescent brains may be mediated by sustained inhibition of insulin/IGF-1 signaling needed for cell survival, neuronal plasticity, and myelin maintenance.
authors: Departments of Pathology (Neuropathology), Neurology, Neurosurgery & Medicine and the Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School at Brown University, Providence, RI.
authors: Alexandra
authors: A
authors: Ewenczyk
authors: Departments of Pathology (Neuropathology), Neurology, Neurosurgery & Medicine and the Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School at Brown University, Providence, RI.
authors: Jason
authors: J
authors: Ziplow
authors: Departments of Pathology (Neuropathology), Neurology, Neurosurgery & Medicine and the Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School at Brown University, Providence, RI.
authors: Ming
authors: M
authors: Tong
authors: Departments of Pathology (Neuropathology), Neurology, Neurosurgery & Medicine and the Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School at Brown University, Providence, RI.
authors: Tran
authors: T
authors: Le
authors: Departments of Pathology (Neuropathology), Neurology, Neurosurgery & Medicine and the Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School at Brown University, Providence, RI.
authors: Suzanne M
authors: SM
authors: de la Monte
keywords: Adolescence; Brain development; Brain insulin resistance; Central nervous system; Cerebellum; Fetal alcohol syndrome; Insulin signaling; Motor function; Receptor binding