Tesic Vesna, Perovic Milka, Lazic Divna, Kojic Snezana, Smiljanic Kosara, Ruzdijic Sabera, Rakic Ljubisav, Kanazir Selma
Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
J Steroid Biochem Mol Biol. 2015 May;149:43-52. doi: 10.1016/j.jsbmb.2015.01.013. Epub 2015 Jan 20.
Diminished glucocorticoid signaling is associated with an age-related decline in hippocampal functioning. In this study we demonstrate the effect of intermittent, every other day (EOD) feeding on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar rats. In aged ad libitum-fed rats, a decrease in the level of total GR and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged rats subjected to EOD feeding, starting from 6 months of age, showed an increase in GR and pGR levels and a higher content of hippocampal corticosterone. Furthermore, prominent nuclear staining of pGR was observed in CA1 pyramidal and DG granule neurons of aged EOD-fed rats. These changes were accompanied by increased Sgk-1 and decreased GFAP transcription, pointing to upregulated transcriptional activity of GR. EOD feeding also induced an increase in the expression of the mineralocorticoid receptor. Our results reveal that intermittent feeding restores impaired GR signaling in the hippocampus of aged animals by inducing rather than by stabilizing GR signaling during aging.
糖皮质激素信号减弱与海马功能随年龄增长而下降有关。在本研究中，我们证明了隔日（EOD）间歇性喂养对中年（18个月大）和老年（24个月大）Wistar大鼠海马中糖皮质激素/糖皮质激素受体（GR）系统的影响。在老年自由进食大鼠中，检测到总GR水平和丝氨酸（Ser）232位点磷酸化的GR（pGR）水平降低。相反，从6个月大开始接受EOD喂养的老年大鼠，其GR和pGR水平增加，海马皮质酮含量更高。此外，在老年EOD喂养大鼠的CA1锥体神经元和齿状回颗粒神经元中观察到pGR显著的核染色。这些变化伴随着Sgk-1增加和GFAP转录减少，表明GR的转录活性上调。EOD喂养还诱导盐皮质激素受体表达增加。我们的结果表明，间歇性喂养通过诱导而非在衰老过程中稳定GR信号，恢复了老年动物海马中受损的GR信号。
