Villa R F, Ferrari F, Gorini A
Department of Biology and Biotechnology, Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, University of Pavia, Via Ferrata, 9, 27100 Pavia, Italy.
Department of Biology and Biotechnology, Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, University of Pavia, Via Ferrata, 9, 27100 Pavia, Italy.
Neuroscience. 2013 Sep 17;248:414-26. doi: 10.1016/j.neuroscience.2013.06.027. Epub 2013 Jun 25.
The maximum rate (Vmax) of some enzymatic activities related to energy consumption was evaluated in synaptic plasma membranes from rat brain striatum, the synaptic energy state being a crucial factor in neurodegenerative diseases etiopathogenesis. Two types of synaptic plasma membranes were isolated from rats subjected to in vivo treatment with L-acetylcarnitine at two different doses (30 and 60 mg × kg(-1) i.p., 28 days, 5 days/week). The following enzyme activities were evaluated: acetylcholinesterase (AChE); Na(+), K(+), Mg(2+)-ATP-ase; ouabain insensitive Mg(2+)-ATP-ase; Na(+), K(+)-ATP-ase; direct Mg(2+)-ATP-ase; Ca(2+), Mg(2+)-ATP-ase; and low- and high-affinity Ca(2+)-ATP-ase. In control (vehicle-treated) animals, enzymatic activities are differently expressed in synaptic plasma membranes type I (SPM1) with respect to synaptic plasma membranes type II (SPM2), the evaluated enzymatic activities being higher in SPM2. Subchronic treatment with L-acetylcarnitine decreased AChE on SPM1 and SPM2 at the dose of 30 mg × kg(-1). Pharmacological treatment decreased ouabain insensitive Mg(2+)-ATP-ase activity and high affinity Ca(2+)-ATP-ase activity at the doses of 30 and 60 mg × kg(-1) respectively on SPM1, while it decreased Na(+), K(+)-ATP-ase, direct Mg(2+)-ATP-ase and Ca(2+), Mg(2+)-ATP-ase activities at the dose of 30 mg × kg(-1) on SPM2. These results suggest that the sensitivity to drug treatment is different between these two populations of synaptic plasma membranes from the striatum, confirming the micro-heterogeneity of these subfractions, possessing different metabolic machinery with respect to energy consumption and utilization and the regional selective effect of L-acetylcarnitine on cerebral tissue, depending on the considered area. The drug potential effect at the synaptic level in Parkinson's Disease neuroprotection is also discussed with respect to acetylcholine and energy metabolism.
在大鼠脑纹状体的突触质膜中评估了一些与能量消耗相关的酶活性的最大速率(Vmax),突触能量状态是神经退行性疾病发病机制中的关键因素。从接受两种不同剂量(30和60 mg×kg⁻¹腹腔注射,28天,每周5天)L-乙酰肉碱体内治疗的大鼠中分离出两种类型的突触质膜。评估了以下酶活性:乙酰胆碱酯酶(AChE);Na⁺、K⁺、Mg²⁺-ATP酶;哇巴因不敏感的Mg²⁺-ATP酶;Na⁺、K⁺-ATP酶;直接Mg²⁺-ATP酶;Ca²⁺、Mg²⁺-ATP酶;以及低亲和力和高亲和力Ca²⁺-ATP酶。在对照(接受载体治疗)动物中,I型突触质膜(SPM1)与II型突触质膜(SPM2)中的酶活性表达不同,评估的酶活性在SPM2中更高。L-乙酰肉碱亚慢性治疗在30 mg×kg⁻¹剂量下降低了SPM1和SPM2上的AChE。药物治疗在30和60 mg×kg⁻¹剂量下分别降低了SPM1上哇巴因不敏感的Mg²⁺-ATP酶活性和高亲和力Ca²⁺-ATP酶活性,而在30 mg×kg⁻¹剂量下降低了SPM2上的Na⁺、K⁺-ATP酶、直接Mg²⁺-ATP酶和Ca²⁺、Mg²⁺-ATP酶活性。这些结果表明,纹状体中这两种突触质膜群体对药物治疗的敏感性不同,证实了这些亚组分的微观异质性,在能量消耗和利用方面具有不同的代谢机制,以及L-乙酰肉碱对脑组织的区域选择性作用,这取决于所考虑的区域。还讨论了该药物在帕金森病神经保护中突触水平的潜在作用与乙酰胆碱和能量代谢的关系。