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Coupling of MR visible GABA, glutamate and glutamine to metabolic and neuronal pathways

Coupling of MR visible GABA, glutamate and glutamine to metabolic and neuronal pathways. Navid Seraji-Bozorgzad. Selective Serotonin Reuptake Inhibitors (SSRI) are widely used in treatment of depression, and other psychiatric disorders.

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Coupling of MR visible GABA, glutamate and glutamine to metabolic and neuronal pathways

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  1. Coupling of MR visible GABA, glutamate and glutamine to metabolic and neuronal pathways Navid Seraji-Bozorgzad

  2. Selective Serotonin Reuptake Inhibitors (SSRI) are widely used in treatment of depression, and other psychiatric disorders. • Further understanding of the acute effects of SSRI has important clinical implications. In the beginning (circa 2004)… There was serotonin. HR-MAS 1H-MRS Neurochemical profile of rats 1 hr after treatment with Citalopram. (n=8)

  3. Problems • MR visible GABA, GLU, and GLN are more representative of the total pool, rather than released pool. • The predominant pathways (large effects) are most probably metabolic rather than neuronal. The interaction between the two makes the interpretation further complicated. What role, if any, does MRS play in understanding the neurobiology of psychopharmacological agents (besides phenomenology)?

  4. Probing the GABA circuits with gabaculine (-) Is there a neuronal component to the MRS findings? Gabaculine increased GABA levels 2-3 folds in all brain regions. The increase, however, was region dependant (highest in cortical v. subcortical regions) Gabaculine also decreased glutamine levels in HC and AST. Correlations analysis confirmed an inverse GLN – GABA relation.

  5. …MRS can aid in understanding neurobiology. Gabaculine says…

  6. For the Future • Use of more sophisticated regional analysis to probe neurocircuitry using MRS (e.g. PLS) • Use of antagonists to confirm proposed neuronal components. • Return to the SSRI data with a better understanding of MRS measures of GABA, glutamate and glutamine.

  7. Acknowledgments • My advisor: Dr. Galloway • Our pre-clinical neuroimaging lab: Shonagh, Kerry, Kristen2, Saugy, Jenn • The BRAINS group, and Dept. Psychiatry for support. Special thanks to Dr. Haacke and the people of Harper MR Center.

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