Variability of mitochondrial energy balance across brain regions

Brain is not homogenous and neurons from various brain regions are known to have different vulnerabilities to mitochondrial mutations and mitochondrial toxins. However, it is not clear if this vulnerability is connected to different energy metabolism in specific brain regions. Here, using live-cell imaging, we compared mitochondrial membrane potential and nicotinamide adenine dinucleotide (NADH) redox balance in acute rat brain slices in different brain regions and further detailed the mitochondrial metabolism in primary neurons and astrocytes from rat cortex, midbrain and cerebellum. We have found that mitochondrial membrane potential is higher in brain slices from the hippocampus and brain stem. In primary co-cultures, mitochondrial membrane potential in astrocytes was lower than in neurons, whereas in midbrain cells it was higher than in cortex and cerebellum. The rate of NADH production and mitochondrial NADH pool were highest in acute slices from midbrain and midbrain primary neurons and astrocytes. Although the level of adenosine tri phosphate (ATP) was similar among primary neurons and astrocytes from cortex, midbrain and cerebellum, the rate of ATP consumption was highest in midbrain cells that lead to faster neuronal and astrocytic collapse in response to inhibitors of ATP production. Thus, midbrain neurons and astrocytes have a higher metabolic rate and ATP consumption that makes them more vulnerable to energy deprivation.