Department of Neurobiology, Institute for Biological Research 'Siniša Stanković' - National Institute of Republic of Serbia, University of Belgrade Belgrade, Serbia.
Nutr Neurosci. 2022 Mar;25(3):537-549. doi: 10.1080/1028415X.2020.1769410. Epub 2020 Jun 1.
Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young and middle aged people. Food restriction (FR) has been shown to act neuroprotectively in animal models of stroke and TBI. Indeed, our previous studies showed that FR attenuates inflammation, through suppression of microglial activation and TNF-α production, suppresses caspase-3-induced neuronal cell death and enhances neuroplasticity in the rat model of TBI. Glucocorticoids (GCs) play a central role in mediating both molecular and behavioral responses to food restriction. However, the exact mechanisms of FR neuroprotection in TBI are still unclear. The goal of the present study was to examine whether FR exerts its beneficial effects by altering the glucocorticoid receptor (GR) signaling alone and/or together with other protective factors.
To this end, we examined the effects of FR (50% of regular daily food intake for 3 months prior to TBI) on the protein levels of total GR, GR phosphoisoform Ser232 (p-GR) and its transcriptional activity, as well as 11β-HSD1, NFκB (p65) and HSP70 as factors related to the GR signaling.
Our results demonstrate that FR applied prior to TBI significantly changes p-GR levels, and it's transcriptional activity during the recovery period after TBI. Moreover, as a pretreatment, FR modulates other protective factors in response to TBI, such as 11β-HSD1, NF-κB (p65) and HSP70 that act in parallel with GR in it's anti-inflammatory and neuroprotective effects in the rat model of brain injury.
Our results suggest that prophylactic FR represents a potent non-invasive approach capable of changing GR signalling, together with other factors related to the GR signaling in the model of TBI.
创伤性脑损伤（TBI）是中青年人群中最常见的神经损伤原因之一。已证明，在中风和 TBI 的动物模型中，饮食限制（FR）具有神经保护作用。事实上，我们之前的研究表明，FR 通过抑制小胶质细胞激活和 TNF-α产生来减轻炎症，抑制 TBI 大鼠模型中的 caspase-3 诱导的神经元细胞死亡，并增强神经可塑性。糖皮质激素（GCs）在介导对饮食限制的分子和行为反应中起核心作用。然而，FR 在 TBI 中的神经保护的确切机制仍不清楚。本研究的目的是研究 FR 是否通过单独改变糖皮质激素受体（GR）信号转导，或与其他保护因子一起发挥其有益作用。
为此，我们研究了 FR（TBI 前 3 个月将日常食物摄入量减少 50%）对总 GR、GR 磷酸化异构体 Ser232（p-GR）及其转录活性以及与 GR 信号转导相关的 11β-HSD1、NFκB（p65）和 HSP70 的蛋白水平的影响。
我们的结果表明，FR 在 TBI 前应用可显著改变 p-GR 水平及其在 TBI 后恢复期间的转录活性。此外，作为预处理，FR 调节其他与 TBI 相关的保护因子，如 11β-HSD1、NF-κB（p65）和 HSP70，它们与 GR 一起在脑损伤大鼠模型中发挥抗炎和神经保护作用。
我们的结果表明，预防性 FR 代表了一种有效的非侵入性方法，能够改变 GR 信号转导，以及与 TBI 模型中与 GR 信号转导相关的其他因素。
