The stress system in the human brain in depression and neurodegeneration

Swaab, Dick F.; Bao, Ai-Min; Lucassen, Paul J.

doi:10.1016/j.arr.2005.03.003

Cited by 839 publications

(559 citation statements)

References 379 publications

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“…Infusion of BDNF into the hippocampus area produced antidepressant-like behavioral effects in rats (Shirayama et al, 2002). Therefore, it is indicated that BDNF is an important factor in the pathogenesis of depression, and increasing BDNF levels might be a common pathway for antidepressants to exert therapeutic functions (Swaab et al, 2005). In the present study, the results demonstrated that treatment with PSY reversed the CUMS-induced reduction of BDNF mRNA expression and protein levels in the hippocampus of rats.…”

Section: Discussionsupporting

confidence: 55%

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Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Gao

et al. 2017

Journal of Ethnopharmacology

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Ethnopharmacological relevance: There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. Materials and Methods:In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action.The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. Results:The results showed that PS extracts (100, 200 mg/kg) and PSY (12.5, 25, 50 mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20 mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. Conclusions:These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus.

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Section: Discussionsupporting

confidence: 55%

“…It is reported that the response to stress is mediated by the HPA axis, which is considered an important pathway in the pathogenesis of depression (Swaab et al, 2005). A potent stressor can activate the HPA axis hyperactivity, leading to the release of CORT into the blood.…”

Section: Discussionmentioning

confidence: 99%

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Gao

et al. 2017

Journal of Ethnopharmacology

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“…Oestrogen replacement after ovariectomy has been shown to increase SERT mRNA and SERT availability in female rats [33] and in hypothalamic regions of female macaques [34]. Depressed women may have significantly higher 24-h mean levels of diurnal oestradiol rhythms, and may have higher testosterone levels than healthy individuals [35]. Testosterone may increase SERT availability by conversion to oestrogen by aromatase, which is especially available in the diencephalon.…”

Section: Methodological Explanations For Inconsistent Findingsmentioning

confidence: 99%

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Ruhé

Booij

Reitsma

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods We included 49 depressed outpatients (mean±SD 42.3±8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [ 123 I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP ND ) in the midbrain and diencephalon with cerebellar binding as a reference. Results In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p=0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p=0.002) and an additional smoking×gender (p=0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p=0.018) with higher SERT availability in winter. Conclusion Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

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“…In particular, the involvement of the hippocampus in depression and suicidal behavior has been inferred from studies revealing morphological changes of this structure in response to stress hormones, although these changes may often be reversible markers of an ongoing stress or depression-related process. 32 Also, postmortem examinations have produced a large body of evidence supporting the implication of limbic areas in suicide. Molecular studies in postmortem hippocampi of suicides have pointed to altered levels of 5-HT2A receptor, 33 cyclic AMP (cAMP) response element-binding, 34 extracellular signal-regulated kinase1/2 mitogen-activated protein (MAP) kinases, 35,36 protein kinase C isozymes.…”

Section: Introductionmentioning

confidence: 99%

Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

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The stress system in the human brain in depression and neurodegeneration

Cited by 839 publications

References 379 publications

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Patterns of gene expression in the limbic system of suicides with and without major depression

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