EFFECT OF N-STEAROYLETHANOLAMINE ON THE LIPID COMPOSITION OF THE FRONTAL CORTEX AND HIPPOCAMPUS OF THE RAT'S BRAIN AT THE AGING

K. S. Romanenko
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Abstract

Aim. To study the possible protective effect of cannabimimetic lipid - N-stearoylethanolamine (NSE) on the lipid composition of the frontal cortex, hippocampus and on the state of episodic memory of old rats. Methods. Extraction of lipids from the tissues of the hippocampus and frontal cortex of rats was performed by the method of Bligh and Dyer. Phospholipids were separated by two-dimensional thin layer chromatography. Methyl esters of fatty acids from lipid extract were obtained by a modified method of Carreau and Dubaco. Quantitative analysis of fatty acid methyl esters was performed by gas-liquid chromatography on an Agilent GC7890 chromatograph with an Agilent 8987 mass detector. The fractions of free and esterified cholesterol were separated by one-dimensional thin layer chromatography. The dry cholesterol residue was analyzed on a Carlo Erba gas-liquid chromatograph. Results. The study of the diacyl (DF) and plasmalogen (PF) forms of phospholipids (PLs) content in the frontal cortex and hippocampus have shown a significant decrease in the plasmalogen form of PE (Phosphatidylethanolamine) (up to 15%) and an increase in its DF, compare to its content in young rats. Administration of NSE to old rats led to a significant increase in PF PE and did not cause significant changes in the content of PF in the composition of other PL of the frontal cortex of the brain and hippocampus. The decrease in the percentage of various phospholipids was found in frontal cortex and hippocampus of old rats: the content of phosphatidylcholine (PC) and phosphatidylinositol (PI) was significantly reduced in the frontal cortex and the decrease of diphosphatidylglycerol (DPG), PI and phosphatidylserine (PS) was found in the hippocampus, compare to the young animals. Administration of NSE to old rats had a different effects on the content of various phospholipids. The increase in the content of PC and PI in the frontal cortex and PS and DPG in the hippocampus is particularly pronounced due to NSE. An increase in the content of saturated fatty acids (FFAs ) and a decrease in the content of unsaturated FFAs in the frontal cortex and hippocampus of old rats also has been found. It has also been found that NSE administration to old rats promoted the growth of the free cholesterol level in the frontal cortex and hippocampus. The results of the New Object Recognition test in old rats have shown that a short-term memory has been improved by NSE. Conclusions. The administration of NSE to old rats causes an increase in PF of PLs in the frontal cortex and hippocampus of the brain, which can be considered as one of the mechanisms of neuroprotective action of NSE in aging. The changes in the phospholipids and fatty acids composition, and free cholesterol level of the frontal cortex and hippocampus of the brain of old rats caused by NSE administration have been shown to be adaptive and restorative. The New Object Recognition Behavioral Test has shown that NSE restores short-term memory in older rats. The obtained results expand the understanding of the mechanisms of biological action of NSE during aging in mammals and create the basis for the development a new drug with geroprotective properties.
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N-硬脂酰乙醇胺对衰老大鼠大脑额叶皮层和海马脂质组成的影响
目标研究拟大麻脂-N-硬脂酰乙醇胺(NSE)对老年大鼠额叶皮层、海马脂质组成及情景记忆状态的可能保护作用。方法。采用Bligh和Dyer法从大鼠海马和额叶皮层组织中提取脂质。磷脂的分离采用二维薄层色谱法。采用改良的Carreau和Dubaco方法从脂质提取物中提取脂肪酸甲酯。脂肪酸甲酯的定量分析通过气-液色谱法在安捷伦GC7890色谱仪上用安捷伦8987质量检测器进行。通过一维薄层色谱法分离游离胆固醇和酯化胆固醇的组分。在Carlo-Erba气相色谱仪上分析干燥的胆固醇残留物。后果对额叶皮层和海马中二酰基(DF)和磷脂酰(PF)形式的磷脂(PL)含量的研究表明,与年轻大鼠的含量相比,磷脂酰乙醇胺(PE)的磷脂酰形式显著减少(高达15%),其DF增加。对老年大鼠施用NSE导致PF PE显著增加,并且没有导致大脑额叶皮层和海马体的其他PL组成中PF含量的显著变化。老年大鼠的额叶皮层和海马中发现各种磷脂的百分比降低:与年轻动物相比,额叶皮层中的磷脂酰胆碱(PC)和磷脂酰肌醇(PI)含量显著降低,海马中的二磷脂酰甘油(DPG)、PI和磷脂酰丝氨酸(PS)含量降低。老年大鼠给予NSE对各种磷脂含量有不同的影响。由于NSE,额叶皮层中PC和PI以及海马中PS和DPG含量的增加尤其明显。还发现老年大鼠额叶皮层和海马中饱和脂肪酸(FFAs)含量增加,不饱和FFAs含量降低。研究还发现,老年大鼠服用NSE可促进额叶皮层和海马游离胆固醇水平的增长。在老年大鼠中进行的新物体识别测试结果表明,NSE改善了短期记忆。结论。老年大鼠给予NSE可导致大脑额叶皮层和海马中PL的PF增加,这可被认为是NSE在衰老中的神经保护作用机制之一。NSE给药引起的老年大鼠大脑额叶皮层和海马的磷脂和脂肪酸组成以及游离胆固醇水平的变化已被证明是适应性和恢复性的。新物体识别行为测试表明,NSE可以恢复老年大鼠的短期记忆。所获得的结果扩展了对NSE在哺乳动物衰老过程中的生物学作用机制的理解,并为开发具有促性腺激素保护特性的新药奠定了基础。
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