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| Roberto Federico Villa |
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Department of Physiological Pharmacological Sciences, university of Pavia, piazza Botta, 11 27100 Pavia
e-mail: rfvilla@unipv.it |
Poster Presentation: |
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| REGIONAL MITOCHONDRIAL ENERGY METABOLISM OF CEREBRAL TISSUE DURING AGEING. |
| Villa and A. Gorini | |
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Department of Physiological Pharmacological Science - Laboratory of Neurochemistry and molecular Medicine - University of Pavia - Piazza Botta, 11 - 27100 Pavia (italy)s |
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| The Vmax of the enzymes related to energy metabolism was evaluated in non-synaptic and intra-synaptic mitochondria from different functional areas of cerebral tissue of rats aged 6, 12, 18, 22 and 26 months. The following enzymes were evaluated: citrate synthase, malate dehydrogenase and succinate dehydrogenase, representative of Kreb's cycle metabolism, NADH-cytochrome c reductase (integrated activity of Complex I-III) and cytochrome oxidase (Complex IV), representative of the electron transfer chain efficiency.
The activities of these enzymes were differently expressed in non-synaptic, free perikaryal mitochondria respect to intra-synaptic ones in 6 months-old rats, emphasizing an intrinsic characterization of energy-linked metabolic pathways of free respect to intra-synaptic mitochondria. In addition, in a density gradient, the intra-synaptic mitochondria may be separated in "heavy" and "light" ones, possessing a very different catalytic activities of the enzymes, underlying the special micro-heterogeneity of mitochondria in Central Nervous System.
When these enzymes related to energy transduction of mitochondria taken from different functional areas of brain were evaluated, a regional, area-related energy metabolism picture clearly emerges, indicating the macro-heterogeneity of metabolic attitude of single brain areas. This observation is also true when different parts of the cerebral cortex are considered, for example the right hemisphere mitochondria versus left hemisphere ones or versus frontal cerebral cortex mitochondria, both of non-synaptic and intra-synaptic origin. The metabolic and catalytic activity of these enzyme is different when these activities are studied in various animal species (rat, monkey).
Age-related differences of Vmax of all enzymes were observed, but these modifications are very complex: for example, citrate synthase activity decreased at 12, 18, 26 months, while malate dehydrogenase increased at 12, 18 months, only in specific areas, while these differences are never seen in other areas; succinate dehydrogenase was unaffected by age only in a limited number of areas; the electron transfer chain enzyme NADH-cytochrome c reductase (Complex I-III) increased at 12, 18, 26 months, while cytochrome oxidase (Complex IV) decreased particularly at 12 months in cerebral cortex mitochondria, but the activity of this key-enzyme was never affected in different types of mitochondria in different areas.
On the whole, all these data indicate that these enzyme activities, that are biochemical parameters of functional significance, undergo diversificated changes of activity during ageing and that each cerebral area possess its own specific metabolic profile for these enzymes, indicating a particular specificity of energy transduction mechanisms, linked to brain physiological efficiency. These effects of ageing on non-synaptic and intra-synaptic mitochondrial enzyme activities appear to be possible relevant factors both for "steady-state" metabolic rate in physiological brain, as well as of pathological brain, expecially when the neurodegenerative diseases linked to ageing are considered.
Therefore, we think that a comprehensive inter-species study of these enzymatic systems applied to the human brain areas using our available technologies, appears to be of great importance for the understanding the physiophatology of human brain diseases, expecially of those related to ageing.
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