Altered Expression of p53 mRNA in the Brain and Pituitary During Repeated Immobilization Stress: Negative Correlation with Glucocorticoid Receptor mRNA Levels

Nishimura, Kanae; Makino, Shinya; Tanaka, Yasushi; Kaneda, Tadafumi; Hashimoto, Kozo

doi:10.1111/j.1365-2826.2004.01131.x

Cited by 30 publications

(23 citation statements)

References 51 publications

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“…It has previously been reported that unstressed prepubertal and adult males have similar levels of hippocampal GR mRNA [36], and the present results support these findings. In addition, our data indicate that prepubertal animals also exhibit a similar decrease in hippocampal GR expression in response to acute stress in both dorsal and ventral hippocampus, as has been previously reported for adults [12,13,14,15,16]. Unlike the reported down-regulation of GR typically observed in response to acute stress, chronic stress does not commonly alter GR expression in adults [37].…”

Section: Discussionsupporting

confidence: 56%

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Glucocorticoid Receptor mRNA Expression in the Hippocampal Formation of Male Rats before and after Pubertal Development in Response to Acute or Repeated Stress

et al. 2007

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Numerous studies have established that adolescence is marked by substantial changes in stress reactivity and hippocampal function. Glucocorticoid receptors (GRs) in the hippocampus are imperative in corticosterone-dependent gene transcription when glucocorticoid levels are relatively high, such as during periods of stress. As reported previously, in reaction to acute stress, prepubertal animals show a significantly more protracted corticosterone response compared to adults. Chronic stress, however, results in a higher peak response, but a faster return to baseline in prepubertal compared to adult animals. Thus, depending on the developmental stage and experience of the animal, the hippocampus is exposed to different concentrations and durations of corticosterone. The present set of experiments assessed the effects of acute or repeated stress on GR mRNA expression in the dorsal and ventral hippocampal formation either before or after pubertal maturation in male rats. We found that acute stress results in a significant decrease in GR mRNA in the CA1 pyramidal cell layer and dentate gyrus in the dorsal and ventral hippocampal formation of both prepubertal and adult males. In response to repeated stress, we found no differences in GR expression in either the dorsal or ventral hippocampus. Thus, despite the dramatic differences in corticosterone concentration following stress at these two developmental stages, the stress-induced changes in GR expression in the hippocampus before and after pubertal maturation were more similar than different. These data point to a dissociation between differential stress-induced corticosterone responses and regulation of hippocampal GR levels in prepubertal and adult animals.

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Section: Discussionsupporting

confidence: 56%

“…In adults, hippocampal GR expression is generally decreased in response to stress [12,13,14,15,16]. However, it is presently unknown whether acute or chronic stress may differentially affect GR levels in the hippocampal formation of prepubertal compared to adult animals.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Receptor mRNA Expression in the Hippocampal Formation of Male Rats before and after Pubertal Development in Response to Acute or Repeated Stress

et al. 2007

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“…Of interest to the current study are reports demonstrating that a 3-day restraint stress paradigm decreased Bcl-2 immunoreactivity in the hippocampus, whereas poststress 1-or 3-week olanzapine treatment reversed the decrease in the intensity of Bcl-2 staining to pre-stress levels; Bcl-xl and Bax were not examined (Luo et al, 2004). In other reports, repeated immobilization stress increased mRNA expression of the tumor suppressor gene p53 in hippocampal subfields (Nishimura et al, 2004) and decreased Bcl-2 mRNA expression in the hippocampus (Yun et al, 2003). Increased Bcl-2 immunoreactivity in the hippocampus has also been observed following chronic treatment with the antidepressants, amitriptyline and venlafaxine (Xu et al, 2003).…”

Section: Introductionmentioning

confidence: 68%

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Kosten

Galloway

Duman

et al. 2007

Neuropsychopharmacol

148

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Apoptosis has been proposed as a contributing cellular mechanism to the structural alterations that have been observed in stress-related mood disorders. Antidepressants, on the other hand, are hypothesized to exert trophic and/or neuroprotective actions. The present study examined the regulation of the major antiapoptotic (Bcl-2, Bcl-xl) and proapoptotic (Bax) genes by repeated unpredictable stress (an animal model of depression) and antidepressant treatments (ADT). In adult rats, exposure to unpredictable stress reduced Bcl-2 mRNA levels in the central nucleus of the amygdala (CeA), cingulate (Cg), and frontal (Fr) cortices. Bcl-xl mRNA was significantly decreased in hippocampal subfields. In contrast, chronic administration of clinically effective antidepressants from four different classes, ie fluoxetine, reboxetine, tranylcypromine, and electroconvulsive seizures (ECS) upregulated Bcl-2 mRNA expression in the Cg, Fr, and CeA. Reboxetine, tranylcypromine, and ECS selectively increased Bcl-xl, but not Bcl-2 mRNA expression in the hippocampus. Chemical ADT but not ECS, robustly enhanced Bcl-2 expression in the medial amygdaloid nucleus and ventromedial hypothalamus. Fluoxetine did not influence Bcl-xl expression in the hippocampus, but it was the only ADT that decreased Bax expression in this region. In the CeA, again in direct contrast to the stress effects, exposure to all classes of ADTs significantly increased Bcl-2 mRNA. The selective regulation of Bcl-xl and Bax in hippocampal subfields and of Bcl-2 in the Cg cortex, amygdala, and hypothalamus suggests that these cellular adaptations contribute to the long-term neural plastic adaptations to stress and ADTs in cortical, hypothalamic, and limbic brain structures.

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“…Subsequent works to elucidate the effect of stress on GR expression have been unable to identify a common effect of stress on GR expression in the hippocampus. Conflicting studies have shown GR mRNA levels to remain stable [10,11,12,13,14] or decrease [10,15,16] after a variety of stressors including forced swimming, restraint, Morris water maze exposure, and novelty stress. Thus far, stress-induced GR mRNA expression has generally been measured by either polymerase chain reaction (PCR) analysis of whole hippocampi [10,13] or via in situ hybridisation [11,12,14,15].…”

Section: Introductionmentioning

confidence: 99%

Rapid Down-Regulation of Glucocorticoid Receptor Gene Expression in the Dentate Gyrus after Acute Stress in vivo: Role of DNA Methylation and MicroRNA Activity

et al. 2016

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Background: Although glucocorticoid receptors (GRs) in the hippocampus play a vital role in the regulation of physiological and behavioural responses to stress, the regulation of receptor expression remains unclear. This work investigates the molecular mechanisms underpinning stress-induced changes in hippocampal GR mRNA levels in vivo. Methods: Male Wistar rats were killed either under baseline conditions or after forced swim stress (FSS; 15 min in 25°C water). Rat hippocampi were micro-dissected (for mRNA, microRNA, and DNA methylation analysis) or frozen whole (for chromatin immunoprecipitation). In an additional experiment, rats were pre-treated with RU486 (a GR antagonist) or vehicle. Results: FSS evoked a dentate gyrus-specific reduction in GR mRNA levels. This was related to an increased DNMT3a protein association with a discreet region of the Nr3c1 (GR gene) promoter, shown here to undergo increased DNA methylation after FSS. FSS also caused a time-dependent increase in the expression of miR-124a, a microRNA known to reduce GR mRNA expression, which was inversely correlated with a reduction in GR mRNA levels 30 min after FSS. FSS did not affect GR binding to a putative negative glucocorticoid response element within the Nr3c1 gene. Conclusions: Acute stress results in decreased GR mRNA expression specifically in the dentate gyrus. Our results indicate that a complex interplay of multiple molecular mechanisms - including increased DNA methylation of discrete CpG residues within the Nr3c1 gene, most likely facilitated by DNMT3a, and increased expression of miR-124a - could be responsible for these changes.

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Altered Expression of p53 mRNA in the Brain and Pituitary During Repeated Immobilization Stress: Negative Correlation with Glucocorticoid Receptor mRNA Levels

Cited by 30 publications

References 51 publications

Glucocorticoid Receptor mRNA Expression in the Hippocampal Formation of Male Rats before and after Pubertal Development in Response to Acute or Repeated Stress

Glucocorticoid Receptor mRNA Expression in the Hippocampal Formation of Male Rats before and after Pubertal Development in Response to Acute or Repeated Stress

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Rapid Down-Regulation of Glucocorticoid Receptor Gene Expression in the Dentate Gyrus after Acute Stress in vivo: Role of DNA Methylation and MicroRNA Activity

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