Department of Physiology of Ontogenesis, Institute of Biology, Kharkov Karazin National University, 4 Svobody pl., 61077 Kharkov, Ukraine.
Department of Physiology of Ontogenesis, Institute of Biology, Kharkov Karazin National University, 4 Svobody pl., 61077 Kharkov, Ukraine.
Arch Gerontol Geriatr. 2014 May-Jun;58(3):420-6. doi: 10.1016/j.archger.2013.12.005. Epub 2013 Dec 27.
Abnormalities of sphingolipid turnover in the brain during normal aging and age-related neurological disorders were associated with the neurons loss and cognitive malfunction. Calorie restriction (CR) prevented age-related deficits in hippocampal long-term potentiation and improved cognitive function at old age. In the paper we investigated the ceramide and sphingomyelin (SM) levels in the brain regions, which are critical for learning and memory of 3- and 24-month-old rats, as well as the correction of sphingolipid turnover in the brain of old rats, by means of the CR diet and modulators of SM turnover. Using the [methyl-(14)C-choline]SM, the neutral, but not the acid SMase activity has been observed to increase in both the hippocampus and brain cortex of 24-month-old rats with respect to 3-month-old animals. Age-dependent changes of neutral SMase activities were associated with ceramide accumulation and SM level drop in the brain structures studied. Treatment of the rats with the CR diet or N-acetylcysteine (NAC) or α-tocopherol acetate, but not an inhibitor of acid SMase imipramine, reduced the ceramide content and neutral SMase activity in the hippocampus of 24-month-old animals with respect to control rats of the same age. These results suggest that redox-sensitive neutral SMase plays important role in SM turnover dysregulation in both the hippocampus and neocortex at old age and that the CR diet can prevent the age-dependent accumulation of ceramide mainly via neutral SMase targeting.
在正常衰老和与年龄相关的神经紊乱过程中，大脑中神经酰胺和鞘磷脂（SM）代谢的异常与神经元丢失和认知功能障碍有关。热量限制（CR）可预防海马长时程增强与年龄相关的缺陷，并改善老年时的认知功能。在本文中，我们研究了 3 个月和 24 个月大的大鼠的大脑中对学习和记忆至关重要的脑区中的神经酰胺和鞘磷脂（SM）水平，以及通过 CR 饮食和 SM 代谢调节剂来纠正老年大鼠的大脑中的鞘磷脂代谢。使用 [甲基-（14）C-胆碱]SM，我们观察到相对于 3 个月大的动物，24 个月大的大鼠的海马体和大脑皮层中的中性 SM 酶活性而非酸性 SM 酶活性均增加。中性 SM 酶活性的年龄依赖性变化与研究的脑结构中的神经酰胺积累和 SM 水平下降有关。用 CR 饮食或 N-乙酰半胱氨酸（NAC）或α-生育酚乙酸酯处理大鼠，但不是酸性 SM 酶抑制剂丙咪嗪，与同年龄的对照大鼠相比，可降低 24 个月大的动物海马体中的神经酰胺含量和中性 SM 酶活性。这些结果表明，氧化还原敏感的中性 SM 酶在老年时海马体和新皮层的 SM 代谢失调中起重要作用，并且 CR 饮食可以通过靶向中性 SM 酶来主要预防与年龄相关的神经酰胺积累。
