Neuroprotective effects of food restriction in a rat model of traumatic brain injury - the role of glucocorticoid signaling.
Mladenović Đorđević, Aleksandra
Article (Accepted Version)
© 2020 Informa UK Limited, trading as Taylor & Francis Group
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OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.
This is an Accepted Manuscript of an article published by Taylor & Francis in Nutritional Neuroscience on 01 Jun 2020, available online: http://www.tandfonline.com/10.1080/1028415X.2020.1769410.
Keywords:Brain injury; GR signaling; HSP70; NF-kB; 11-βHSD1; Food restriction; Glucocorticoids; Neuroprotection
Source:Nutritional Neuroscience, 2020