Uticaj dugotrajne restrikcije hrane na ekspresiju glukokortikoidnog receptora u prednjem mozgu pacova tokom starenja
The effect of long-term food restriction on te expression of glucocorticoid receptor in the rat forebrain during aging
Doctoral thesis (Published version)
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Moderate restriction in food intake (dietary restriction, DR) extends the life-span anddelays the onset of many age-related diseases. In addition, food-restricted animals exhibitattenuated cognitive deficits during aging as they perform better in learning and memory tasksthan their ad libitum fed counterparts. At the same time, the animals on chronic food restrictionhave elevated levels of plasma corticosterone, which implies that this treatment could beconsidered as a mild stressor. So far, there are no literature data regarding the effects of foodrestriction on glucocorticoid signaling in the brain during aging and the mechanisms by whichDR exhibits its neuroprotective effects are poorly understood. Two brain regions of interest arecortex and hippocampus, regions particularly prone to age-related changes. The same regions arealso involved in cognition and regulation of the hypothalamic–pituitary–adrenal (HPA) axisactivity.The aim of the present study was to evaluate the effect of long-term food restriction onglucocorticoid signaling pathway in the cortex and hippocampus of rats during aging.Experimental animals (male Wistar rats, 6 months old) were divided into two groups. The ALgroup was fed ad libitum, whereas the food restricted group (DR) received 100% of the meandaily intake of the AL animals every other day. The animals were examined at the age of 18 and24 months. Six-month-old animals were used as a control. Glucocorticoid signaling in specificbrain regions was examined at the pre-receptor level, as well as regarding the level of expressionand glucocorticoid receptor activity by using immunoassays, Western blot, PCR andimmunohistochemistry.The results of this study demonstrate an age-related increase in cortical corticosteroneconcentration. The increase in the hormone level was further detected in DR animals, in bothbrain regions examined. However, 11β-HSD1, a key enzyme in brain tissue that regulates theavailability of corticosterone to its receptors, was increased only in the hippocampi of AL ratsand in the cortex of rats subjected to the long-term food restriction. The most pronouncedchanges in the level of glucocorticoid receptor during aging were observed in the hippocampi of AL animals...
Keywords:Long-term food restriction; Aging; Glucocorticoid hormones; 11β-HSD1; Glucocorticoid receptor; Cortex; Hippocampus
Source:University of Belgrade, Faculty of Biology, 2015, 1-101