THRESHOLD EFFECTS IN SYNAPTOSOMAL AND NONSYNAPTIC MITOCHONDRIA FROM HIPPOCAMPAL CA1 AND PARAMEDIAN NEOCORTEX BRAIN-REGIONS

After a brief period of global ischemia, the hippocampal CAI region is more susceptible to irreversible damage than the paramedian neocortex . To test whether primary differences in bioenergetic parameters may b e present between these regions, respiration rates and respiratory con trol activities were measured. In synaptosomal and nonsynaptic mitocho ndria isolated from the hippocampal CA1 region, state 3 respiration ra tes and complex IV activities were significantly lower than those pres ent in synaptosomal and nonsynaptic mitochondria from the paramedian n eocortex. These results suggest that mitochondria from the CA1 hippoca mpal area differ in some properties of metabolism compared with the ne ocortex area, which may render them more susceptible to a toxic insult such as that of ischemia. In addition, when complex I and IV activiti es were titrated with specific inhibitors, thresholds in ATP synthesis and oxygen respiration became apparent. Complex I and IV activities w ere decreased by 60% in nonsynaptic mitochondria from the hippocampal CA1 region and paramedian neocortex before oxidative phosphorylation w as severely compromised; however, in synaptosomes from these regions, complex I activities had a threshold of 25%, indicating heterogenous b ehaviour for brain mitochondria. Reduced complex I thresholds in mitoc hondria, in association with other constitutive defects in energy meta bolism, may induce a decreased ATP supply in the synaptic region. The implications of these findings are discussed in relation to delayed ne uronal death and processes of neurodegeneration.