A biphasic regulation of receptor mRNA expressions for growth hormone, glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute stress

Fujikawa, Takahiko; Soya, Hideaki; Fukuoka, Hidenori; Alam, Khorshed S. M.; Yoshizato, Hideo; McEwen, Bruce S.; Nakashima, Kenichiro

doi:10.1016/s0006-8993(00)02576-2

Cited by 48 publications

(33 citation statements)

References 36 publications

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“…PTSD is a complex disorder showing a spectrum of severity. To get the most informative view of the core phenotype, we focused, for this comparison, on the difference between subjects exhibiting the consistent phenotype (subjects with full persistent PTSD (1-8 Table 1) and subjects showing no PTSD criteria at any time (14)(15)(16)(17)(18)(19) (Figure 1a). When only M4 samples were analyzed, all subjects were classified into two clusters, one containing PTSD subjects and the other control subjects (Figure 1b).…”

Section: Gene Expression Patterns Discern Ptsd Statusmentioning

confidence: 99%

“…Acute stress exposure has been shown to induce long-term expression differences in the rat brain for cholinergic 15 and neuroendocrine genes. 16,17 While direct sampling of the brain is not possible in humans, peripheral blood cell gene expression may provide a surrogate indicator of differential response to stress and subsequent PTSD. Supporting this tenet, acute psychological stress is associated with immune activation, 18 and persistent immune alterations have been linked with chronic PTSD.…”

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confidence: 99%

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Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

et al. 2005

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Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results. Molecular Psychiatry (2005) 10, 500-513.

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Section: Gene Expression Patterns Discern Ptsd Statusmentioning

confidence: 99%

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confidence: 99%

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

et al. 2005

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“…In addition, the DG is highly responsive to stress (Bear and Abraham, 1996;Camodeca et al, 1998;Huang et al, 1999;Fujikawa et al, 2000;Ahmed et al, 2006), and modulation of DG function can readily influence spatial performance in the MWM Roy, 1993, 1995;Vaher et al, 1994;Xavier et al, 1999). We have shown here that gene delivery into DG can protect against stress-mediated impairment of spatial performance.…”

Section: Discussionmentioning

confidence: 67%

Enhancing Cognition after Stress with Gene Therapy

Nicholas¹,

Munhoz²,

Ferguson³

et al. 2006

J. Neurosci.

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Hippocampal function is essential for the acquisition, consolidation, and retrieval of spatial memory. High circulating levels of glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, have been shown to impair both acquisition and retrieval and can either impair or enhance consolidation, depending on experimental conditions. In contrast, estrogen can enhance spatial memory performance and can block the deleterious effects of GCs on such performance. We therefore constructed a chimeric gene ("ER/GR") containing the hormone-binding domain of the GC receptor and the DNA binding domain of the estrogen receptor; as a result, ER/GR transduces deleterious GC signals into beneficial estrogenic ones. We show here that acute immobilization stress, before acquisition and retrieval phases, increases latencies for male rats in a hidden platform version of the Morris water maze. This impairment is blocked by hippocampal expression of the ER/GR transgene. ER/GR expression also blocks decreases in platform crossings caused by acute stress, either after acquisition or before retrieval. Three days of stress before acquisition produces an estrogen-like enhancement of performance in ER/GR-treated rats. Moreover, ER/GR blocks the suppressive effects of GCs on expression of brain-derived neurotrophic factor (BDNF), a growth factor central to hippocampal-dependent cognition and plasticity, instead producing an estrogenic increase in BDNF expression. Thus, ER/GR expression enhances spatial memory performance and blocks the impairing effects of GCs on such performance.

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“…In contrast, acute stress downregulated Gr in the dentate gyrus (DG) and the CA1 region of the hippocampus. 21,22 Methylation of CpG 16 in the core of the Ngfi-a binding site has previously been shown to affect the regulation of Gr 1 7 transcripts by Ngfi-a. This CpG site was rarely methylated in the hippocampus of offspring of high caring mothers, but highly methylated (> 80%) after low maternal care.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of theglucocorticoid receptorpromoter 1₇in adult rats

et al. 2012

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A biphasic regulation of receptor mRNA expressions for growth hormone, glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute stress

Cited by 48 publications

References 36 publications

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

Enhancing Cognition after Stress with Gene Therapy

Epigenetic regulation of theglucocorticoid receptorpromoter 1₇in adult rats

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A biphasic regulation of receptor mRNA expressions for growth hormone, glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute stress

Cited by 48 publications

References 36 publications

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

Enhancing Cognition after Stress with Gene Therapy

Epigenetic regulation of theglucocorticoid receptorpromoter 17in adult rats

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Epigenetic regulation of theglucocorticoid receptorpromoter 1₇in adult rats