Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
Neurochem Int. 2012 Dec;61(8):1424-32. doi: 10.1016/j.neuint.2012.10.009. Epub 2012 Oct 23.
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.
研究了衰老和胞苷二磷酸胆碱治疗（20mg/kg 体重腹腔注射，28 天）对雄性 Wistar 大鼠大脑前额皮质非突触和突触内“轻”和“重”线粒体中与三羧酸循环（柠檬酸合酶、α-酮戊二酸脱氢酶、苹果酸脱氢酶）、谷氨酸和相关氨基酸代谢（谷氨酸脱氢酶、谷氨酸-草酰乙酸-和谷氨酸-丙酮酸转氨酶）相关的代表性线粒体酶最大速率（V（max））的影响。在衰老过程中，酶活性以复杂的方式随线粒体的类型而变化，即非突触和突触内。这种微异质性是一个重要的因素，因为与能量相关的线粒体酶催化特性会导致脑内组织体内具有生理病理学意义的代谢改变，还可以区分药物的突触前和突触后作用部位，并影响组织对有害刺激的反应性。结果表明，胞苷二磷酸胆碱体内治疗在 18 个月时选择性地增强大脑的能量代谢，特别是修饰非突触和突触内“轻”线粒体亚群中的酶催化活性。这证实了衰老过程中观察到的酶催化活性变化反映了每个单一年龄的生物能量状态和相应的能量需求，进一步证明了体内药物治疗能够干扰神经元的能量代谢。
