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

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

• Navid Seraji-Bozorgzad

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• In the beginning (circa 2004)
• There was serotonin.

• 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.

HR-MAS 1H-MRS Neurochemical profile of rats 1 hr
after treatment with Citalopram. (n8)
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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)?

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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.
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MRS can aid in understanding neurobiology.
Gabaculine says
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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.

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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.