BACKGROUND: Millions of Americans suffer from Alzheimer's Disease (AD), which is characterized by significant neurological impairment and an accumulation in brain tissue of senile plaques consisting of beta amyloid (Abeta) peptide. The hippocampus, a region primarily responsible for learning and memory, appears to be particularly susceptible to AD-related injury and chronic alcohol abuse. Although certain risk factors for AD are known, it is unclear if alcohol abuse or dependence may contribute to neuropathology in AD. Recent research suggests that low-to-moderate consumption of alcohol may protect against development of AD, while alcohol dependence may increase risk of developing AD. Therefore, the current studies aimed to investigate the effects of exposure to 50 or 100 mM ethanol (EtOH) and withdrawal on hippocampal injury induced by Abeta peptide treatment. METHODS: The present studies exposed organotypic hippocampal slice cultures to 50 or 100 mM ethanol (EtOH) for 10 days, after which the slices underwent ethanol withdrawal (EWD) in the presence of varying concentrations of Abeta 25-35 (0.1, 1, 10 microM), or 35-25 (200 microM), a negative control reverse sequence peptide. Cellular injury, as evidenced by uptake of propidium iodide (PI), was assessed for each subregion of the hippocampal complex (CA1, CA3, and dentate gyrus). RESULTS: Cellular injury in the CA1 pyramidal cell layer was significantly increased during withdrawal from exposure to 100 mM, but not 50 mM, EtOH. Exposure to Abeta in ethanol-naïve cultures did not produce significant cytotoxicity. However, exposure to Abeta during EWD from 100 mM produced marked increases in CA1 pyramidal cell region cytotoxicity, effects reversed by cotreatment with a nontoxic concentration of the NMDA receptor channel blocker MK-801 (20 microM). CONCLUSIONS: These data suggest that withdrawal from exposure to a high concentration of EtOH produces marked cellular injury in the hippocampus, particularly the CA1 subregion. Further, this EtOH exposure and withdrawal regimen sensitizes the hippocampus to the toxic effects of Abeta treatment in a manner reflecting over activity of NMDA receptor function.
BACKGROUND: Millions of Americans suffer from Alzheimer's Disease (AD), which is characterized by significant neurological impairment and an accumulation in brain tissue of senile plaques consisting of beta amyloid (Abeta) peptide. The hippocampus, a region primarily responsible for learning and memory, appears to be particularly susceptible to AD-related injury and chronic alcohol abuse. Although certain risk factors for AD are known, it is unclear if alcohol abuse or dependence may contribute to neuropathology in AD. Recent research suggests that low-to-moderate consumption of alcohol may protect against development of AD, while alcohol dependence may increase risk of developing AD. Therefore, the current studies aimed to investigate the effects of exposure to 50 or 100 mM ethanol (EtOH) and withdrawal on hippocampal injury induced by Abeta peptide treatment. METHODS: The present studies exposed organotypic hippocampal slice cultures to 50 or 100 mM ethanol (EtOH) for 10 days, after which the slices underwent ethanol withdrawal (EWD) in the presence of varying concentrations of Abeta 25-35 (0.1, 1, 10 microM), or 35-25 (200 microM), a negative control reverse sequence peptide. Cellular injury, as evidenced by uptake of propidium iodide (PI), was assessed for each subregion of the hippocampal complex (CA1, CA3, and dentate gyrus). RESULTS:Cellular injury in the CA1 pyramidal cell layer was significantly increased during withdrawal from exposure to 100 mM, but not 50 mM, EtOH. Exposure to Abeta in ethanol-naïve cultures did not produce significant cytotoxicity. However, exposure to Abeta during EWD from 100 mM produced marked increases in CA1 pyramidal cell region cytotoxicity, effects reversed by cotreatment with a nontoxic concentration of the NMDA receptor channel blocker MK-801 (20 microM). CONCLUSIONS: These data suggest that withdrawal from exposure to a high concentration of EtOH produces marked cellular injury in the hippocampus, particularly the CA1 subregion. Further, this EtOH exposure and withdrawal regimen sensitizes the hippocampus to the toxic effects of Abeta treatment in a manner reflecting over activity of NMDA receptor function.
Authors: Elvis Cuevas; Hector Rosas-Hernandez; Susan M Burks; Manuel A Ramirez-Lee; Aida Guzman; Syed Z Imam; Syed F Ali; Sumit Sarkar Journal: Metab Brain Dis Date: 2019-07-02 Impact factor: 3.584
Authors: Katherine J Smith; Tracy R Butler; Rachel L Self; Brittany B Braden; Mark A Prendergast Journal: Brain Res Date: 2007-10-18 Impact factor: 3.252
Authors: Tracy R Butler; Katherine J Smith; Jennifer N Berry; Lynda J Sharrett-Field; Mark A Prendergast Journal: Alcohol Alcohol Date: 2009-09-16 Impact factor: 2.826
Authors: Tracy R Butler; Katherine J Smith; Rachel L Self; Brittany B Braden; Mark A Prendergast Journal: Alcohol Clin Exp Res Date: 2008-07 Impact factor: 3.455
Authors: Katherine J Smith; Rachel L Self; Tracy R Butler; Michael M Mullins; Layla Ghayoumi; Robert C Holley; John M Littleton; Mark A Prendergast Journal: Brain Res Date: 2007-05-04 Impact factor: 3.252