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Shonagh O’Leary-Moore Departments of Psychiatry and Psychology

Acute Ethanol Exposure Alters the Metabolomic Profile in Rat Brain as Measured by High Resolution Magic Angle Spinning 1 H Magnetic Resonance Spectroscopy (HRMAS 1 H-MRS). Shonagh O’Leary-Moore Departments of Psychiatry and Psychology. Acute Alcohol Exposure-Neurobiology.

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Shonagh O’Leary-Moore Departments of Psychiatry and Psychology

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  1. Acute Ethanol Exposure Alters the Metabolomic Profile in Rat Brain as Measured by High Resolution Magic Angle Spinning 1H Magnetic Resonance Spectroscopy (HRMAS 1H-MRS) Shonagh O’Leary-Moore Departments of Psychiatry and Psychology

  2. Acute Alcohol Exposure-Neurobiology • Enhances GABA-A activated Cl- Influx • NMDA receptor antagonist • Potentiates 5HT3 receptors, CA+2 channel (EtOH actually probably inhibits most voltage gated ion channels) • Stimulates DA release • Differential susceptibility in various brain regions due to distribution of various receptor subtypes From: Oscar-Bermas & Marinovic, Alcohol Research and Health, 27, 125, 2003. Purpose: Determine the regional metabolic profile in rat brain following a binge exposure to alcohol using HR-MAS 1H MRS and HPLC.

  3. OCC CBV HIP PST For HPLC SN VTA BS Experimental Design & Methods n = 18, Male Sprague-Dawley Rats, ~250-300 g Subjects intubated with either 0 or 6 g/kg of 20% w/v of ethanol 1st intubation (0 or 3 g/kg EtOH) 2nd intubation (0 or 3 g/kg EtOH) 6 hr – Post EtOH blood and tissue collection 2 hr – Post EtOH and control blood and tissue collection HRMAS and HPLC BAC peak (225-300 mg/dl)

  4. Spectral Processing- LCModel Quantification of Data and Custom Peak Fitting Algorithms for EtOH Comparison of Control and Ethanol-exposed spectra from the PST The presence of EtOH was clearly evident in all brain regions sampled

  5. Neurochemical Profile of Acute Alcohol Exposure in the PST * HVA/DA ratios * ** * Acute EtOH increases DA turnover in the PST 2 hours after exposure * * * RESULTS - Traditional Univariate Analyses of Neurochemical Data Neurochemical Profile of Acute Alcohol Exposure in all regions Increase with alcohol Decrease with alcohol

  6. Principal Component Analyses • Uses all of the variance from a data set • Finds linear combinations of variables that account for maximum variance • Components are uncorrelated (PC1 does not correlate with PC2) PC1 PC1 accounted for ~21% of the variability in the data set and significantly distinguished control from alcohol exposed subjects (p < 0.05) RED – Negatively correlated with PC1 and decreased with acute EtOH exposure GREEN – Positively correlated with PC1 and increased with acute EtOH exposure

  7. Summary/Conclusions • Acute EtOH alters the metabolic profile measured by HRMAS • Brain EtOH levels can be seen and quantified by HRMAS • EtOH exposure increased DA turnover, increased glutamine levels in the PST, BS, and HIP and decreased GABA in the MDT. • Additional effects were seen in membrane phospholipids (PEA and GPC) • PCA is useful to analyze HRMAS data Acknowledgements: Dr. Matthew Galloway Dr. John Hannigan Navid Seraji-Bozorgzad Kristen Prevost NIAAA F31 AA015224-01

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