Long-term dietary restriction differentially affects the expression of BDNF and its receptors in the cortex and hippocampus of middle-aged and aged male rats.
Long-term dietary restriction differentially affects the expression of BDNF and its receptors in the cortex and hippocampus of middle-aged and aged male rats.
复制标题
长期饮食限制对中老年雄性大鼠皮质和海马BDNF及其受体表达的影响存在差异。
DOI：
10.1007/s10522-014-9537-9
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发表时间：
2015
期刊：
影响因子：
4.5
通讯作者：
Kanazir,Selma
中科院分区：
文献类型：
--
作者：
Smiljanic,Kosara;Pesic,Vesna;MladenovicDjordjevic,Aleksandra;Pavkovic,Zeljko;Brkic,Marjana;Ruzdijic,Sabera;Kanazir,Selma
饮食限制（DR）在包括人类在内的许多生物体的衰老和与年龄相关的疾病方面发挥了显着的有益作用。本研究旨在研究长期DR对中年（12月龄）和老年（24月龄）雄性Wistar大鼠皮层和海马BDNF系统在转录和翻译水平的影响。结果显示，DR上调了两个区域中外显子特异性BDNF转录物的表达，随后仅在中年动物的皮质中升高了mBDNF水平。在老年动物中，DR通过增加proBDNF和降低mBDNF水平来调节BDNF蛋白水平。此外，在DR后的中年大鼠中观察到全长TrkB水平升高，伴随着糖基化程度较低的TrkB蛋白水平降低，而在老年大鼠中，DR仅扩增了糖基化程度较低的TrkB的表达。磷酸化TrkBY 816的水平在老化过程中是稳定的，无论喂养。在中年DR喂养的动物的两个区域中检测到p75 NTR水平降低，而在老年DR喂养的大鼠的皮质中检测到显著增加。这些发现进一步阐明了DR作为BDNF系统的调节剂，揭示了其在中年和老年动物中的不同作用。鉴于proBDNF/BDNF回路水平表达在不同脑功能和行为的各个方面的重要性，有必要进一步阐明所应用的饮食方案与动物年龄有关的最佳持续时间，以达到其最有利的效果。
Dietary restriction (DR) exerts significant beneficial effects in terms of aging and age-related diseases in many organisms including humans. The present study aimed to examine the influence of long-term DR on the BDNF system at the transcriptional and translational levels in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. The obtained results revealed that the DR upregulated the expression of exon-specific BDNF transcripts in both regions, followed by elevated levels of mBDNF only in the cortex in middle-aged animals. In aged animals, DR modulated BDNF protein levels by increasing proBDNF and by declining mBDNF levels. Additionally, elevated levels of the full-length TrkB accompanied by a decreased level of the less-glycosylated TrkB protein were observed in middle-aged rats following DR, while in aged rats, DR amplified only the expression of the less-glycosylated form of TrkB. The levels of phosphorylated TrkBY816were stable during aging regardless of feeding. Reduced levels of p75NTRwere detected in both regions of middle-aged DR-fed animals, while a significant increase was measured in the cortex of aged DR-fed rats. These findings shed additional light on DR as a modulator of BDNF system revealing its disparate effects in middle-aged and aged animals. Given the importance of the proBDNF/BDNF circuit-level expression in different brain functions and various aspects of behavior, it is necessary to further elucidate the optimal duration of the applied dietary regimen with regard to the animal age in order to achieve its most favorable effects.