Sustained Impairments in Brain Insulin/Igf Signaling in Adolescent Rats Subjected to Binge Alcohol Exposure during DevelopmentAlexandra Ewenczyk, Jason Ziplow, Ming Tong, Tran Leand Suzanne M. de la Monte*
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
- *Corresponding Author:
- Suzanne M. de la Monte, MD, MPH
Pierre Galletti Research Building
Rhode Island Hospital, 55 Claverick Street
Room 419, Providence, RI 02903, USA
E-mail: [email protected]
Received Date: January 07, 2012; Accepted Date: February 06, 2012; Published Date: February 10, 2012
Citation: Ewenczyk A, Ziplow J, Tong M, Le T, de la Monte SM (2012) Sustained Impairments in Brain Insulin/Igf Signaling in Adolescent Rats Subjected to Binge Alcohol Exposures during Development. J Clinic Experiment Pathol 2:106. doi: 10.4172/2161-0681.1000106
Copyright: © 2012 Ewenczyk A et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Aims:Using an early postnatal (3rd trimester 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.