program outline

Opening Lecture: Bioenergetics and oxidative stress in cell culture models of neuronal cell death 

                             
Session 1. Integration of oxidative and glycolytic metabolism
This session focuses on roles of major energy-producing pathways during activation in vivo and in vitro; the roles of lactate as fuel or regulatory agent will be emphasized.
Topics:
. Astrocyte activation in working brain
. Fueling cerebral activity in exercising humans
. Coupling of glycolysis and respiration by nitric oxide

. Compartmentation of glycolysis and glycogenolysis

  Monocarboxylate transporters: adapting energy supply to neurons under all circumstances

Session 2. From supplier to consumer: Glucose distribution and regulation of glucose-glycogen is more complex than thought
This session focuses on complexity of glucose supply-demand relationships and emerging regulatory mechanisms involved in provision, storage, and compartmentation of fuel for activated brain cells.
Topics:
. Cellular distributions of glucose transporters
. Regulation of glucose transporters in astrocytes and neurons
. Glucose, your intracellular signaling molecule
. Neurobarrier coupling in the brain: adjusting glucose entry with demand


Session 3. Imaging the cellular redox potential in vivo
This and the following session examine the key roles of redox molecules in regulation of metabolism, linking cytoplasm and mitochondrial activity, and imaging of local functional metabolism in action in situ.
Topics:

. Cell type distribution of the malate-aspartate shuttle: influence on brain glucose metabolism.

  Brain Mitochondrial Transporters: What's known, What we need to know
. Role of the mitochondrial aspartate-glutamate carrier aralar

Session 4. Controlling and imaging the cellular redox potential in vivo

Topics:

.Synaptic stimulation and mechanisms of NADH / Flavin dynamics in brain slices
. Redox switching: modulation of glucose and pyruvate/lactate metabolism

.pH and flavin imaging in vivo

Redoc switching: modulation of glucose and pyruvate/lactate metabolism

Session 5. Mitochondrial roles in excitotoxicity and disease
This session examines the critical role of mitochondria in life and death; their function extends well beyond that of providing energy oxidatively.
Topics:
. Mitochondrial dysfunction in hybrid lines expressing genes from patients with mitochondrial disorders
. The dark side of sugar: glucose-induced superoxide production in neurons
. Sources of reactive oxygen species: from enzymes to in situ mitochondria
. Reactive oxygen species: generation and protection

Session 6. Novel aspects of glutamate transmission and homeostasis
Glutamate is a "bi-functional transmitter" involved in cross-talk between neurons and astrocytes, in addition to its key roles in energy metabolism.
Topics:

. Vesicular uptake coupled to glycolysis
. The glutamate-glutamine cycle is not stoichiometric: fates of glutamate
. Contribution of astrocytes to synaptic transmission in the rat supraoptic nucleus 
. Pyruvate carboxylation and recycling: making and breaking of glutamate 

Session 7. Metabolic control analysis and metabolomics
Metabolic modeling and evaluation of patterns of metabolite composition and concentration are key to tissue and cellular profiling to identify flux changes, responses to drugs, and disturbances in disease processes .
Topics:
. High resolution NMR and metabolomics 
. Metabolic NMR data and modelling
. Modeling of compartmentalized energy metabolism

Closing Lecture: Metabolomics: quantitative assessment of metabolic response to diet