Behavioral alterations induced by post-weaning isolation rearing of rats are accompanied by reduced VGF/BDNF/TrkB signaling in the hippocampus

Chmelova, Magdalena; Balagova, Lucia; Marko, Martin; Vrankova, Stanislava; Cebová, Martina; Ježová, Daniela; Riečanský, I; Hlavacova, Natasa

doi:10.1016/j.neuint.2019.104473

Cited by 22 publications

(14 citation statements)

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“…The results of behavioral measurements in the present study are fully in agreement with the well‐known anxiogenic effects of chronic social isolation starting early in life, which were mainly described in male rodents. As this study was performed in female rats, the results add further support to increased anxiety‐like behavior, reflected by both traditional spatiotemporal and ethological indices of anxiety induced by social isolation in females 35,36 …”

Section: Discussionsupporting

confidence: 64%

“…As this study was performed in female rats, the results add further support to increased anxiety-like behavior, reflected by both traditional spatiotemporal and ethological indices of anxiety induced by social isolation in females. 35,36 We have shown previously that chronic pharmacological blockade of MRs exerts an anxiolytic action 37 and a mild antidepressant-like effect. 38 Spironolactone treatment in this study failed to modify classical spatiotemporal measures of anxiety, namely the frequency and time spent in the open arms of the maze.…”

Section: Discussionmentioning

confidence: 99%

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Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life

Karailiev

Hlavacova

Chmelova

et al. 2021

Neurogastroenterology Motil

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Background: Simultaneous evaluation of barrier protein expression in the gut and the brain and their modulation under stress conditions have not been studied before now. As the permeability and function of the gut and blood-brain barrier are different and both express the MRs, we hypothesized that stress of post-weaning social isolation induces changes in tight junction protein expression in the gut which are (1) independent of changes in the brain and (2) are mediated via the mineralocorticoid receptor (MR).Methods: First, using UPLC-MS/MS we have successfully validated and selected a dose (1.2 mg/rat/day) of the MR antagonist spironolactone to treat female rats exposed to stress of chronic isolation or control conditions from postnatal day 21 for 9 weeks. Key Results: Isolation stress caused an enhancement of gene expression of occludin and ZO-1 and a decrease in claudin-5 and MR expression in both the small intestine and prefrontal cortex. Isolation stress failed to decrease claudin-5 (small intestine) and MR (prefrontal cortex) gene expression in spironolactone-treated rats. MR blockade resulted in a decrease in claudin-15 expression in the small intestine. Anxiogenic effect of chronic stress, measured in elevated plus-maze test, was partly prevented by spironolactone treatment. Conclusions & Inferences:Claudins, the main regulators of intestinal barrier permeability responded to chronic stress of social isolation and/or simultaneous blockade of MR in female rats by alterations independent of changes in the brain cortex. The results suggest a physiological role of MR in the control of claudin expression in the small intestine, but not in the brain cortex.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life

Karailiev

Hlavacova

Chmelova

et al. 2021

Neurogastroenterology Motil

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“…BDNF was observed also in studies investigating the consequences of exposure to PS, particularly those using protocols including situational trauma reminder to simulate post-traumatic stress symptoms [26,27]. In a recent study, stress of post-weaning isolation did not alter hippocampal BDNF, but it led to a reduced gene expression of VGF (non-acronymic) and tyrosine receptor kinase B (TrkB) receptor [28]. Thus, the modulation of VGF/BDNF/TrkB signaling by repeated PS exposure cannot be excluded.…”

Section: Discussionmentioning

confidence: 93%

Effect of Repeated Predator Scent Exposure on Excitability of Serotonin Neurons and Stress Markers in Rats

Dremencov¹,

Grinchii²,

Buzgoova³

et al. 2021

Preprint

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Exposure to predator scent (PS) has been used aa a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of 5-HT neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawleys rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, the selected electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to repeated PS. Repeated PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

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“…Female Sprague-Dawley rat pups born and handled as described previously (Chmelova et al 2019a(Chmelova et al , 2019b were weaned on postnatal day 21. The pups were exposed to stress of chronic social isolation (housing of one rat per cage) or control conditions with social rearing (housing of 3 rats per cage) for 9 weeks.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

“…The pups were exposed to stress of chronic social isolation (housing of one rat per cage) or control conditions with social rearing (housing of 3 rats per cage) for 9 weeks. The details on animals and experimental design were reported previously (Chmelova et al 2019a(Chmelova et al , 2019b. All experimental procedures were approved (approval number Ro-420/15-221) by the Animal Health and Animal Welfare Division of the State Veterinary and Food Administration of the Slovak Republic.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Dopamine concentrations and dopamine receptor gene expression in emotion-related brain structures of female adult rats exposed to stress of chronic isolation from weaning

Karailiev

Hlavacova²,

Chomanic³

et al. 2020

gpb

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It is known that early-life stress events induce profound consequences on emotional brain regions including amygdala, involved in emotional processing and the ventral tegmental area (VTA), which contains neuron cell bodies of the mesolimbic dopaminergic system. The aim of this study is to test the hypothesis that stress induced by long-term social isolation from weaning in female rats is associated with alterations in amygdalar dopamine receptor gene expression and VTA dopamine concentrations. Rats were weaned on postnatal day 21 and then exposed to stress of chronic isolation for 9 weeks. Control animals were housed socially. Amygdalar dopamine D 1 but not D 2 receptor gene expression was decreased in isolated rats compared to controls. Dopamine concentrations in the VTA were enhanced following chronic isolation. A negative correlation was observed between amygdalar D 1 gene expression and dopamine concentrations in the VTA. In conclusion, a reduction of dopamine D 1 receptor gene expression in the amygdala in response to stress induced by chronic isolation in female rats was accompanied by an increase in dopamine concentration in the VTA. Further studies are needed to understand the physiological significance, if any, of negative association of amygdalar dopamine receptor D 1 gene expression and dopamine concentrations in the VTA.

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Behavioral alterations induced by post-weaning isolation rearing of rats are accompanied by reduced VGF/BDNF/TrkB signaling in the hippocampus

Cited by 22 publications

References 50 publications

Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life

Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life

Effect of Repeated Predator Scent Exposure on Excitability of Serotonin Neurons and Stress Markers in Rats

Dopamine concentrations and dopamine receptor gene expression in emotion-related brain structures of female adult rats exposed to stress of chronic isolation from weaning

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