title: Effect of CDP-choline on age-dependent modifications of energy- and glutamate-linked enzyme activities in synaptic and non-synaptic mitochondria from rat cerebral cortex.
abstract: The effect of aging and CDP-choline treatment (20 mg kg⁻¹ body weight i.p. for 28 days) on the maximal rates (V(max)) of representative mitochondrial enzyme activities related to Krebs' cycle (citrate synthase, α-ketoglutarate dehydrogenase, malate dehydrogenase), glutamate and related amino acid metabolism (glutamate dehydrogenase, glutamate-oxaloacetate- and glutamate-pyruvate transaminases) were evaluated in non-synaptic and intra-synaptic "light" and "heavy" mitochondria from frontal cerebral cortex of male Wistar rats aged 4, 12, 18 and 24 months. During aging, enzyme activities vary in a complex way respect to the type of mitochondria, i.e. non-synaptic and intra-synaptic. This micro-heterogeneity is an important factor, because energy-related mitochondrial enzyme catalytic properties cause metabolic modifications of physiopathological significance in cerebral tissue in vivo, also discriminating pre- and post-synaptic sites of action for drugs and affecting tissue responsiveness to noxious stimuli. Results show that CDP-choline in vivo treatment enhances cerebral energy metabolism selectively at 18 months, specifically modifying enzyme catalytic activities in non-synaptic and intra-synaptic "light" mitochondrial sub-populations. This confirms that the observed changes in enzyme catalytic activities during aging reflect the bioenergetic state at each single age and the corresponding energy requirements, further proving that in vivo drug treatment is able to interfere with the neuronal energy metabolism.
authors.affiliation: Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy. robertofederico.villa@unipv.it
authors.forename: Roberto Federico
authors.initials: RF
authors.lastname: Villa
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrari
authors.forename: Antonella
authors.initials: A
authors.lastname: Gorini
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D002952:Citric Acid Cycle / Q000187:drug effects*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004789:Enzyme Activation; D004798:Enzymes / Q000378:metabolism*; D005625:Frontal Lobe / Q000166:cytology* / Q000201:enzymology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004798:Enzymes; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D003566:Cytidine Diphosphate Choline