Freo Ulderico, Dam Mauro, Ori Carlo
Istituto di Anestesiologia e Terapia Intensiva, Dipartimento di Farmacologia e Anestesiologia, Università di Padova, Via C. Battisti, 267, I-35121, Italy.
Brain Res. 2009 Mar 9;1259:32-9. doi: 10.1016/j.brainres.2008.12.025. Epub 2008 Dec 24.
The aim of the present study was to investigate the neuronal structures that mediate the antiaging properties of acetyl-l-carnitine (ALCAR). The regional cerebral metabolic rates for glucose (rCMRglc) have been determined with the quantitative autoradiographic [(14)C]2-deoxyglucose procedure at different times after i.v. administration of saline or ALCAR 500 mg/kg to naïve, non pretreated 3-, 12- and 24-month-old rats and to 24-month-old rats pretreated with ALCAR (100 mg/kg/day, for 3 months). rCMRglc increased maximally at 30 min after ALCAR in 3-, 12- and 24-month old rats (14, 15 and 15 areas affected, 19, 24 and 22% mean increments). Peak metabolic activations occurred with similar magnitude in motor, visual, limbic and thalamic areas in all age rats and with larger magnitude in hippocampal and thalamic areas in aged rats. Cerebral metabolic activations subsided by 60 min after ALCAR in 3-month rats (3 brain regions affected, 4% decrease) and persisted by that time in 12- and 24-month-old rats (14 and 12 regions affected, 15 and 20% increases). Cerebral activations were enhanced in aged rats after chronic treatment with ALCAR (24 brain regions affected, 20% mean increase). Hence, during aging, metabolic responsivity to ALCAR is maintained in most brain areas and increased in limbic and thalamic regions. Increased responsivity to ALCAR may result from undetermined pharmacokinetic factors and/or from a higher sensitivity and contribute to the aging reversal properties of ALCAR.
本研究的目的是调查介导乙酰左旋肉碱（ALCAR）抗衰老特性的神经元结构。通过定量放射自显影[（14）C]2-脱氧葡萄糖程序，在向未处理的3、12和24月龄幼稚大鼠以及用ALCAR（100mg/kg/天，持续3个月）预处理的24月龄大鼠静脉注射生理盐水或500mg/kg ALCAR后的不同时间，测定局部脑葡萄糖代谢率（rCMRglc）。在3、12和24月龄大鼠中，ALCAR给药后30分钟时rCMRglc最大程度增加（分别影响14、15和15个区域，平均增加19%、24%和22%）。在所有年龄的大鼠中，运动、视觉、边缘和丘脑区域均出现了相似程度的峰值代谢激活，而在老年大鼠的海马和丘脑区域激活程度更大。在3月龄大鼠中，ALCAR给药后60分钟时脑代谢激活减弱（3个脑区受影响，降低4%），而在12和24月龄大鼠中此时仍持续存在（分别影响14和12个区域，增加15%和20%）。用ALCAR长期治疗后，老年大鼠的脑激活增强（24个脑区受影响，平均增加20%）。因此，在衰老过程中，大多数脑区对ALCAR的代谢反应性得以维持，而边缘和丘脑区域的反应性增加。对ALCAR反应性的增加可能源于未确定的药代动力学因素和/或更高的敏感性，并有助于ALCAR的抗衰老特性。
