Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression

Wu, Xiaochang; Balesar, Rawien; Lu, Joan; Farajnia, Sahar; Zhu, Qiong-Bin; Huang, Manli; Bao, Ai-Min; Swaab, D.F.

doi:10.1007/s00429-017-1442-y

Cited by 23 publications

(22 citation statements)

References 52 publications

(69 reference statements)

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“…After 5 days in culture, we still detected many viable cells either in slices treated with medium only or medium plus ethanol (Figure ) as we have found in previous studies .…”

Section: Resultssupporting

confidence: 88%

“…To address this putative relationship between CYP17A1 and TrkB we treated post‐mortem human brain slices in short‐term cultures with DHEA (a major product of CYP17A1) or DHEAS. The use of post‐mortem human brain slice cultures was pioneered by our group and it has been established that many cells in the cultured slices remain viable for long periods in vitro . Here, we show that treatment with DHEA increases BDNF mRNA levels in the human brain slices, compared to vehicle‐treated slices.…”

Section: Introductionmentioning

confidence: 63%

“…Tissue, comprising cortical grey matter and a small amount of white matter, was cut in 300 µm thick slices using a McIlwain tissue chopper. Slices were plated in a 24‐well plate and were maintained for a short period (5 days) in culture as previously described with small modifications.…”

Section: Methodsmentioning

confidence: 99%

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Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Luchetti

Verwer

et al. 2017

Brain Pathology

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Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real-time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways. In MDD, a significant decrease in mRNA level of cytochrome P450 17A1 (CYP17A1, synthesizing C19 ketosteroids) in the ACC and a significant increase in mRNA levels of hydroxysteroid sulfotransferase 2A1 [SULT2A1, catalyzing the sulfate conjugation of dehydroepiandrosterone (DHEA)] were observed in the DLPFC, suggesting alterations in DHEA and its sulfate metabolite DHEAS levels. Decreased intensity and distribution of CYP17A1 immunohistochemical staining was found in the ACC of MDD patients. Interestingly, there was a significant positive correlation between the mRNA levels of CYP17A1 and tyrosine-related kinase B (TrkB) full length isoform. In a unique post-mortem human brain slice culture paradigm, BDNF mRNA expression was found to be significantly increased following incubation with DHEA. Together, these data indicate a close relationship between DHEA and BDNF-TrkB pathways in depression. Furthermore, in the DLPFC, higher mRNA levels of 11β-hydroxysteroid dehydrogenase-1 (HSD11B1, reducing cortisone to the active hormone cortisol) and steroidogenic acute regulatory protein (STAR, facilitating the shuttle of cholesterol through the intermembrane space) were found in the MDD patients and BPD patients, respectively. In conclusion, this study suggests the presence of a disturbance in the endogenous synthesis of DHEA and DHEAS in mood disorders, which has a close relationship with BDNF-TrkB signaling.

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“…After 5 days in culture, we still detected many viable cells either in slices treated with medium only or medium plus ethanol (Figure ) as we have found in previous studies .…”

Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 63%

See 1 more Smart Citation

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Luchetti

Verwer

et al. 2017

Brain Pathology

Self Cite

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“…Of note, some studies have suggested a gender difference in plasma AVP levels, despite a lack of consistent findings across all studies. Wu et al reported a significant 253% increase of AVP-ir in female depressed subjects but not in male depressed patients [19]. One study found male controls to have higher peripheral AVP levels compared to female controls, suggesting a possible relationship between sex hormones and AVP [17].…”

Section: Avp and Gendermentioning

confidence: 98%

Does Arginine Vasopressin Reflect HPA-axis Activation in Major Depressive Disorder?

Halaris¹,

Hage²,

Carter³

et al. 2020

CEI

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Researchers have endeavored to subclassify depressive illness based on pathophysiological mechanism. One model relates to hypothalamic-pituitary-adrenal (HPA) axis overactivation with a shift from corticotropin-releasing hormone (CRH) driven regulation to arginine vasopressin (AVP) driven regulation. Given the mixed literature, we compared plasma AVP levels in healthy controls to patients with major depressive disorder (MDD). Plasma samples from 33 patients and 12 controls were collected at baseline, 8 weeks, and 12 weeks of treatment and measured by immunochemical assay. Patients who were treatment responders trended toward lower AVP levels than non-responders. Patients were stratified into low and high AVP groups based on median split. Within the low AVP group, patients whose current episode lasted longer than a year had significantly higher baseline AVP levels than patients whose current episode was less than 6 months. Female patients in the low AVP group had significantly higher baseline AVP levels than male patients. Given the association between stress, HPA axis activation, immune dysregulation, and depression, we also measured concentrations of inflammatory biomarkers. We found a significant negative correlation between IL-10 and baseline AVP levels, within the low AVP subgroup. Given inconsistent data, HPA axis overactivation may be present within a subset of depressed patients.

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“…There is conflicting evidence as to whether the SCN directly modulates mood and anxiety. Several human postmortem brain studies find alterations in specific neurotransmitters and/or receptors in the SCN of individuals with a mood disorder [22][23][24] .…”

Section: Suprachiasmatic Nucleus Regulates Anxiety Behaviormentioning

confidence: 99%

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice

Vadnie

Eberhardt

Hildebrand

et al. 2020

Preprint

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250 words Manuscript: 4,996 words Suprachiasmatic Nucleus Regulates Anxiety Behavior 2 Abstract Circadian rhythms are commonly disrupted in individuals with depression and/or anxiety disorders. Animal studies indicate that circadian rhythm disruption can cause increased depressive and anxiety-like behavior, but the underlying mechanisms are unclear. Currently, there is conflicting evidence as to whether the master pacemaker in the brain, the suprachiasmatic nucleus (SCN), plays a key role in regulating psychiatricrelated behavior. To investigate the role of the SCN in regulating depressive and anxiety-like behavior in mice, we directly manipulated the neural activity of the SCN using two chronic optogenetic stimulation paradigms. Repeated stimulation of the SCN late in the active phase (circadian time 21, CT21) shortened the period and dampened the amplitude of homecage activity rhythms. Repeated stimulation of the SCN at unpredictable times during the dark phase dampened, fragmented and reduced the stability of homecage activity rhythms. In both SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) was associated with increased measures of anxiety-like behavior, but not in control mice. Increased fragmentation and decreased day-to-day stability of homecage activity also correlated with increased anxiety-like behavior. Unexpectedly the change in period of homecage activity rhythms was not directly associated with any psychiatric-related behavior. Furthermore, we did not observe consistent correlations between homecage activity amplitude and depressive-like behavior in stimulated mice. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like, but not depressive-like behavior in mice. This work is an important step in understanding how specific SCN neural activity disruptions affect mood and anxiety-related behavior.

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Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression

Cited by 23 publications

References 52 publications

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Does Arginine Vasopressin Reflect HPA-axis Activation in Major Depressive Disorder?

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice

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