Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect

Morais, Andreia; Mendes-da-Silva, Rosângela Figueiredo; Santos, Eryka Maria dos; Guedes, Rubem Carlos Araújo

doi:10.1016/j.brainres.2014.09.075

Cited by 7 publications

(6 citation statements)

References 67 publications

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“…Prior studies have strongly suggested that GCs, which are major mediators of stress, are the major causal agent of MDD (52,53). Many studies have demonstrated that repeated administration of GCs can induce depressive-like behavior in rodents (54,55). In the present study, we showed that prenatal Dex exposure leads to continuous elevation of GC level in circulation even from E18.…”

Section: Discussionsupporting

confidence: 61%

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

Sheng

et al. 2018

FASEB j.

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Pregnant women at risk of preterm labor usually receive synthetic glucocorticoids (sGCs) to promote fetal lung development. Emerging evidence indicates that antenatal sGC increases the risk of affective disorders in offspring. Data from animal studies show that such disorders can be transmitted to the second generation. However, the molecular mechanisms underlying the intergenerational effects of prenatal sGC remain largely unknown. Here we show that prenatal dexamethasone (Dex) administration in late pregnancy induced depression-like behavior in first-generation (F1) offspring, which could be transmitted to second-generation (F2) offspring with maternal dependence. Moreover, corticotropin-releasing hormone (CRH) and CRH receptor type 1 (CRHR1) expression in the hippocampus was increased in F1 Dex offspring and F2 offspring from F1 Dex female rats. Administration of a CRHR1 antagonist to newborn F1 Dex offspring alleviated depression-like behavior in these rats at adult. Furthermore, we demonstrated that increased CRHR1 expression in F1 and F2 offspring was associated with hypomethylation of CpG islands in Crhr1 promoter. Our results revealed that prenatal sGC exposure could program Crh and Crhr1 gene expression in hippocampus across 2 generations, thereby leading to depression-like behavior. Our study indicates that prenatal sGC can cause epigenetic instability, which increases the risk of disease development in the offspring's later life.-Xu, Y.-J., Sheng, H., Wu, T.-W., Bao, Q.-Y., Zheng, Y., Zhang, Y.-M., Gong, Y.-X., Lu, J.-Q., You, Z.-D., Xia, Y., Ni, X. CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations.

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Section: Discussionsupporting

confidence: 61%

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

Sheng

et al. 2018

FASEB j.

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“…Furthermore, these data extend our knowledge about the actions of taurine and pilocarpine on electrophysiological responses and glial cell reactions, as demonstrated by the CSD-related potentiation of ECoG amplitude and microglial and astrocyte immunoreactivity. The previously described in vivo CSD-induced ECoG potentiation (Lopes-de-Morais et al, 2014;Mendes-da-Silva et al, 2018) has been confirmed in this paper, and its modulation by pilocarpine and taurine has been described (Table 1). Data on anxiety-like behavior, MDA measurements and brain immunohistochemical effects that were produced by taurine and/or pilocarpine treatment represent novel evidence of the action of these compounds on 35-55-day-old rats, whereas data on weight gain, glycemia, and CSD confirm the results of a previous study (Francisco and Guedes, 2018).…”

Section: Discussionsupporting

confidence: 85%

“…The ECoG and the DC (direct current) slow potential variation that is typical of CSD were continuously recorded on the cortical surface (on the intact dura mater) through a digital recording system (Biopac MP 150, Goleta, CA, United States). For each animal, the amplifier’s gain was kept constant over the entire recording session, as previously reported (Lopes-de-Morais et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

“…This algorithm calculates the average amplitude of the ECoG waves. For each animal, the averaged ECoG amplitude was normalized in relation to the lowest sample value, which was considered equal to 1, expressed in relative units and compared before and after the episodes of CSD, as a basis for analyzing the occurrence of potentiation of the spontaneous electrical activity, as reported by our group previously (Lopes-de-Morais et al, 2014; Souza et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

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Taurine/Pilocarpine Interaction in the Malnourished Rat Brain: A Behavioral, Electrophysiological, and Immunohistochemical Analysis

et al. 2019

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This study aimed to evaluate the possible protective role of taurine on anxiety-like behavior, brain electrical activity and glial cell immunoreactivity in well-nourished and malnourished rats that were treated with a subconvulsing dose of pilocarpine. Newborn Wistar rats were subjected to normal or unfavorable lactation conditions, represented by the suckling of litters with 9 or 15 pups, resulting in well-nourished and malnourished animals, respectively. Each nutritional group was split into five subgroups that were treated from postnatal day (PND) 35 to 55 with 300 mg/kg/day of taurine + 45 mg/kg/day of pilocarpine (group T + P), taurine only (group T), pilocarpine only (group P), vehicle control (group V), or not treated control (group naïve; Nv). At PND56-58, the groups were subjected to the elevated plus-maze behavioral tests. Glycemia was measured on PND59. Between PND60 and PND65, the cortical spreading depression (CSD) was recorded in the cerebral cortex, and the levels of malondialdehyde and microglial and astrocyte immunoreactivity were evaluated in the cortex and hippocampus. Our data indicate that treatment with taurine and pilocarpine resulted in anxiolytic-like and anxiogenic behavior, respectively, and that nutritional deficiency modulated these effects. Both treatments decelerated CSD propagation and modulated GFAP- and Iba1-containing glial cells. Pilocarpine reduced body weight and glycemia, and administration of taurine was not able to attenuate the effects of pilocarpine. The molecular mechanisms underlying taurine action on behavioral and electrophysiological parameters in the normal and altered brain remain to be further explored.

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“…Changes with cortical activity have been reported with perinatal dexamethasone. Tapered neonatal dexamethasone in rats alters cortical spreading depression velocity (an evoked propagating wave) in mature animals, but not cortical potentiation [83]. Whilst maternal exposure to dexamethasone in fetal sheep produces changes in EEG power bands lasting at least several days in utero [84], however it is unknown if these changes extend into adulthood, or for more than a few days.…”

Section: Discussionmentioning

confidence: 99%

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

et al. 2016

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The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease.

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Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect

Cited by 7 publications

References 67 publications

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression‐like behavior across 2 generations

Taurine/Pilocarpine Interaction in the Malnourished Rat Brain: A Behavioral, Electrophysiological, and Immunohistochemical Analysis

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

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