Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat

Tešić, Vesna; Perović, Milka; Lazić, Divna; Kojić, Snežana; Smiljanić, Kosara; Ruždijić, Sabera; Rakić, Ljubisav; Kanazir, Selma

doi:10.1016/j.jsbmb.2015.01.013

Cited by 7 publications

(8 citation statements)

References 65 publications

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“…Despite elevated corticosterone levels, anticipated ligand-induced down-regulation of cortical glucocorticoid receptors was not observed in EOD-fed animals. Furthermore, in contrast to our previous results for the hippocampus, where the decrease in GR protein level was obvious and accompanied with EOD-induced increase in mr MRNA during aging [43], no change in both gr and mr mRNA levels was observed in the cortex following long-term FR. The latter is particularly expected, given that MR is less abundant in this brain structure [30].…”

Section: Discussioncontrasting

confidence: 99%

“…The expression profiles of the GRα protein isoforms generated as a result of alternate translation start sites in exon 2 and contributing to complex regulation by glucocorticoids were also performed [46]. As expected, besides the full-length glucocorticoid receptor (97 kDa GR), shorter GRα isoforms (67-, 50-, 40-, and 25-kDa) were detected in rat cortical tissue (Figure 2A), with the 40 kDa isoform being the most prevalent one, as previously reported [43,47]. Quantitative immunoblot analysis also revealed an increase of full-length glucocorticoid receptor (97 kDa GR) in 18-month-old AL rats (68%; * p < 0.05), while in the 24-month-old rats the level of 97 kDa GR was not significantly altered in relation to the level estimated in control, 6-month-old rats (Figure 2B).…”

Section: The Effects Of Aging and Food Restriction On Glucocorticoid Receptor In The Cortexsupporting

confidence: 78%

“…The cortical corticosterone concentrations were determined using competitive enzyme immunoassay (Corticosterone High Sensitivity EIA kit; IDS, East Boldon, UK) according to the manufacturer's instructions, and as previously described [42,43]. In brief, corticosterone in tissue homogenates (in five volumes of 1×PBS) was extracted three times with diethyl ether and combined organic phases were subsequently evaporated and diluted in the assay buffer.…”

Section: Corticosterone Assaymentioning

confidence: 99%

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Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

et al. 2021

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Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser232 were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.

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Section: Discussioncontrasting

confidence: 99%

Section: The Effects Of Aging and Food Restriction On Glucocorticoid Receptor In The Cortexsupporting

confidence: 78%

Section: Corticosterone Assaymentioning

confidence: 99%

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Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

et al. 2021

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“…The GR receptor in the hippocampus is involved in energy homeostasis and stress sensitivity. Diminished glucocorticoid signaling is associated with an age-related decline in hippocampal function, suggesting changes in GR may persist in the long-term [64]. The effects of betaine on GR expression is likely mediated by methylation given that GR is well known to be epigenetically regulated in the brain and influenced by dietary methyl nutrients [65].…”

Section: Betainementioning

confidence: 99%

The Effects of Maternal and Postnatal Dietary Methyl Nutrients on Epigenetic Changes that Lead to Non-Communicable Diseases in Adulthood

Randunu

Bertolo

2020

IJMS

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The risk for non-communicable diseases in adulthood can be programmed by early nutrition. This programming is mediated by changes in expression of key genes in various metabolic pathways during development, which persist into adulthood. These developmental modifications of genes are due to epigenetic alterations in DNA methylation patterns. Recent studies have demonstrated that DNA methylation can be affected by maternal or early postnatal diets. Because methyl groups for methylation reactions come from methionine cycle nutrients (i.e., methionine, choline, betaine, folate), deficiency or supplementation of these methyl nutrients can directly change epigenetic regulation of genes permanently. Although many studies have described the early programming of adult diseases by maternal and infant nutrition, this review discusses studies that have associated early dietary methyl nutrient manipulation with direct effects on epigenetic patterns that could lead to chronic diseases in adulthood. The maternal supply of methyl nutrients during gestation and lactation can alter epigenetics, but programming effects vary depending on the timing of dietary intervention, the type of methyl nutrient manipulated, and the tissue responsible for the phenotype. Moreover, the postnatal manipulation of methyl nutrients can program epigenetics, but more research is needed on whether this approach can rescue maternally programmed offspring.

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“…Cognitive impairment induced by chronic stress refers to the long-term exposure of the body to negative stimuli with intolerance, eventually causing impairment of learning and memory. Under chronic stress, glucocorticoid levels significantly increase, followed by the binding and activation of GRs, resulting in changes in multiple signaling pathways [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic restraint stress impairs cognition via modulating HDAC2 expression

Liu

Zhang

et al. 2021

Translational Neuroscience

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Background To investigate the effects of chronic restraint stress on cognition and the probable molecular mechanism in mice. Methods In the current work, a restraining tube was used as a way to induce chronic stress in mice. The protein levels were determined with ELISA and western blot. A series of behavior tests, including the Morris water maze, elevated plus maze, open field test, and novel object recognition test, were also performed to examine the anxiety and the ability of learning and memory. Moreover, murine neuroblastoma N2a cells were used to confirm the findings from mice under chronic stress. Results Decreased synaptic functions were impaired in chronic stress with the downregulation of PSD95, GluR-1, the neurotrophic factor BDNF, and immediate-onset genes Arc and Egr. Chronic restraint decreased the histone acetylation level in hippocampal neurons while HDAC2 was increased and was co-localized with glucocorticoid receptors. Moreover, chronic stress inhibited the PI3K/AKT signaling pathway and induced energy metabolism dysfunctions. Conclusion This work examining the elevated levels of HDAC2 in the hippocampus may provide new insights and targets for drug development for treating many neurodegenerative diseases.

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Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat

Cited by 7 publications

References 65 publications

Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

The Effects of Maternal and Postnatal Dietary Methyl Nutrients on Epigenetic Changes that Lead to Non-Communicable Diseases in Adulthood

Chronic restraint stress impairs cognition via modulating HDAC2 expression

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