Differential effects of TSPO ligands on mitochondrial function in mouse microglia cells.

Abstract:

:The translocator protein 18 kDa (TSPO), initially characterized as peripheral benzodiazepine receptor, is a conserved outer mitochondrial membrane protein, implicated in cholesterol transport thereby affecting steroid hormone biosynthesis, as well as in general mitochondrial function related to bioenergetics, oxidative stress, and Ca2+ homeostasis. TSPO is highly expressed in steroidogenic tissues such as adrenal glands, but shows low expression in the central nervous system. During various disease states such as inflammation, neurodegeneration or cancer, the expression of mitochondrial TSPO in affected tissues is upregulated. The expression of TSPO can be traced for diagnostic purpose by high affinity radio-ligands. Moreover, the function of TSPO is modulated by synthetic as well as endogenous ligands with agonistic or antagonistic properties. Thus, TSPO ligands serve functions as both important biomarkers and putative therapeutic agents. In the present study, we aimed to characterize the effects of TSPO ligands on mouse BV-2 microglia cells, which express significant levels of TSPO, and analyzed the effect of XBD173, PK11195, and Ro5-4864, as well as the inflammatory reagent Lipopolysaccharides (LPS) on neurosteroid synthesis and on basic mitochondrial functions such as oxidative phosphorylation, mitochondrial membrane potential and Ca2+ homeostasis. Specific TSPO-dependent effects were separated from off-target effects by comparing lentiviral TSPO knockdown with shRNA scramble-controls and wild-type BV-2 cells. Our data demonstrate ligand-specific effects on different cellular functions in a TSPO-dependent or independent manner, providing evidence for both specific TSPO-mediated, as well as off-target effects.

journal_title

Psychoneuroendocrinology

authors

Bader S,Wolf L,Milenkovic VM,Gruber M,Nothdurfter C,Rupprecht R,Wetzel CH

doi

10.1016/j.psyneuen.2019.03.029

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

65-76

eissn

0306-4530

issn

1873-3360

pii

S0306-4530(18)30944-2

journal_volume

106

pub_type

杂志文章
  • Is depression associated with increased oxidative stress? A systematic review and meta-analysis.

    abstract:BACKGROUND:It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes, measures of oxidative DNA and lipid damage respectively, are among the most reliable oxidative stress markers, but studies on their assoc...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1016/j.psyneuen.2014.09.025

    authors: Black CN,Bot M,Scheffer PG,Cuijpers P,Penninx BW

    更新日期:2015-01-01 00:00:00

  • Mineralocorticoid and glucocorticoid receptors and their differential effects on memory performance in people with Addison's disease.

    abstract::The effects of corticosteroids on memory performance have been the subject of some controversy. Whilst many studies have shown that high levels of corticosteroids can impair memory performance, others have shown they can facilitate it. One explanation for these discrepant effects arises from the differential activatio...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章

    doi:10.1016/S0306-4530(03)00103-3

    authors: Tytherleigh MY,Vedhara K,Lightman SL

    更新日期:2004-07-01 00:00:00

  • Lasting Impact of Chronic Adolescent Stress and Glucocorticoid Receptor Selective Modulation in Male and Female Rats.

    abstract::Adolescent animals are vulnerable to the effects of stress on brain development. We hypothesized that long-term effects of adolescent chronic stress are mediated by glucocorticoid receptor (GR) signaling. We used a specific GR modulator (CORT108297) to pharmacologically disrupt GR signaling in adolescent rats during e...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2019.104490

    authors: Cotella EM,Morano RL,Wulsin AC,Martelle SM,Lemen P,Fitzgerald M,Packard BA,Moloney RD,Herman JP

    更新日期:2020-02-01 00:00:00

  • Increased cortisol in women with intimate partner violence-related posttraumatic stress disorder.

    abstract:BACKGROUND:Alterations of hypothalamic-pituitary-adrenal (HPA) axis function and sympathetic-adrenal activity have been proposed as key factors in biological models of posttraumatic stress disorder (PTSD). METHODS:We examined neuroendocrine function in female survivors of intimate partner violence (IPV) with lifetime ...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2006.03.007

    authors: Inslicht SS,Marmar CR,Neylan TC,Metzler TJ,Hart SL,Otte C,McCaslin SE,Larkin GL,Hyman KB,Baum A

    更新日期:2006-08-01 00:00:00

  • Factors contributing to stability and instability in alpha-amylase activity in diluted saliva samples over time.

    abstract::For the measurement of salivary alpha-amylase (sAA) activity, saliva samples first have to be diluted. There is some evidence for instability, that is, a decline of sAA activity in diluted samples. It is not clear which factors during dilution may contribute to this phenomenon and how quickly this decline of sAA activ...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2020.104847

    authors: Skoluda N,Dhrami I,Nater UM

    更新日期:2020-11-01 00:00:00

  • Neuroendocrine and cardiovascular reactions to acute psychological stress are attenuated in smokers.

    abstract::A number of studies have now examined the association between smoking and the magnitude of physiological reactions to acute psychological stress. However, no large-scale study has demonstrated this association incorporating neuroendocrine in addition to cardiovascular reactions to stress. The present study compared ne...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.psyneuen.2014.05.023

    authors: Ginty AT,Jones A,Carroll D,Roseboom TJ,Phillips AC,Painter R,de Rooij SR

    更新日期:2014-10-01 00:00:00

  • Changes in gonadotropin regulation in both behavioral and phenotypic disturbances of sexual differentiation in men.

    abstract::Determinations of gonadotropins and testosterone were performed in 22 men with hypospadias (H), seven male-to-female transsexuals (T) and in 16 normal men (N), all of similar age. The response of serum FSH and LH to GnRH was determined in six subjects in each group. Oligospermia was found in five of 13 patients with H...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/0306-4530(86)90032-6

    authors: Kula K

    更新日期:1986-01-01 00:00:00

  • Cognitive-behavioral stress management buffers decreases in dehydroepiandrosterone sulfate (DHEA-S) and increases in the cortisol/DHEA-S ratio and reduces mood disturbance and perceived stress among HIV-seropositive men.

    abstract::This study examined the effects of a 10-week cognitive-behavioral stress management (CBSM) intervention on dehydroepiandrosterone sulfate (DHEA-S) levels and the ratio of cortisol to DHEA-S (cortisol/DHEA-S), potential surrogate adrenal markers of HIV disease progression, in relation to alterations in mood and distres...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0306-4530(99)00010-4

    authors: Cruess DG,Antoni MH,Kumar M,Ironson G,McCabe P,Fernandez JB,Fletcher M,Schneiderman N

    更新日期:1999-07-01 00:00:00

  • Cerebrospinal fluid and plasma testosterone levels in post-traumatic stress disorder and tobacco dependence.

    abstract:BACKGROUND:Little is known about the relationship between endogenous central nervous system (CNS) testosterone and any psychiatric syndrome. The goal of this study was to screen for potential abnormalities in CNS testosterone levels in patients with post-traumatic stress disorder (PTSD) and/or tobacco dependence. METH...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0306-4530(00)00052-4

    authors: Mulchahey JJ,Ekhator NN,Zhang H,Kasckow JW,Baker DG,Geracioti TD Jr

    更新日期:2001-04-01 00:00:00

  • Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever.

    abstract::The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine a...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.psyneuen.2008.08.016

    authors: Kluge M,Schuld A,Schacht A,Himmerich H,Dalal MA,Wehmeier PM,Hinze-Selch D,Kraus T,Dittmann RW,Pollmächer T

    更新日期:2009-01-01 00:00:00

  • N-terminal pro-atrial natriuretic peptide response to acute exercise in depressed patients and healthy controls.

    abstract:BACKGROUND:The dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in major depression includes hyperactivity and reduced feedback inhibition. Atrial natriuretic peptide (ANP) is able to reduce the HPA-axis response to stress and has an anxiolytic effect in rodents and humans. We hypothesized that patients with de...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.psyneuen.2010.09.009

    authors: Krogh J,Ströhle A,Westrin A,Klausen T,Jørgensen MB,Nordentoft M

    更新日期:2011-06-01 00:00:00

  • Omega-3 and omega-6 fatty acid levels in depressive and anxiety disorders.

    abstract:BACKGROUND:Blood levels of polyunsaturated fatty acids (PUFAs) have been associated to current depression. However, it is unclear whether this association extends to remitted depression and to anxiety disorders. This study examined the relationship of PUFAs with the presence and clinical characteristics of depressive a...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2017.10.005

    authors: Thesing CS,Bot M,Milaneschi Y,Giltay EJ,Penninx BWJH

    更新日期:2018-01-01 00:00:00

  • Hypothalamic-pituitary adrenal response to cholecystokinin-B receptor agonism is resistant to cortisol feedback inhibition.

    abstract::Intravenous injection of the cholecystokinin (CCK)-B receptor agonist, pentagastrin, produces robust, dose-dependent release of adrenocorticotropin (ACTH) and cortisol, supporting the hypothesis that CCK-B agonists pharmacologically activate the hypothalamic-pituitary-adrenal (HPA) axis. The mechanism of activation an...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0306-4530(02)00013-6

    authors: Abelson JL,Young EA

    更新日期:2003-02-01 00:00:00

  • Perceived stress and hair cortisol: Differences in bipolar disorder and schizophrenia.

    abstract:INTRODUCTION:Bipolar disorder (BD) and schizophrenia (SCZ) are psychiatric disorders with shared and distinct clinical and genetic features. In both disorders, stress increases the risk for onset or relapse and dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been reported. The latter is frequently in...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2016.03.010

    authors: Streit F,Memic A,Hasandedić L,Rietschel L,Frank J,Lang M,Witt SH,Forstner AJ,Degenhardt F,Wüst S,Nöthen MM,Kirschbaum C,Strohmaier J,Oruc L,Rietschel M

    更新日期:2016-07-01 00:00:00

  • Signs of sexual behaviour are not increased after subchronic treatment with LHRH in young men.

    abstract::Apart from its action as gonadotropin releasing factor, luteinizing hormone-releasing hormone (LHRH) is a potent regulator of sexual behaviour in animals. The present study aimed to assess a similar role of LHRH for sexuality in humans. In a double-blind placebo-controlled and randomized study, effects of human LHRH a...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0306-4530(00)00031-7

    authors: Perras B,Smolnik R,Fehm HL,Born J

    更新日期:2001-01-01 00:00:00

  • Hippocampal insulin resistance links maternal obesity with impaired neuronal plasticity in adult offspring.

    abstract:OBJECTIVE:Maternal obesity and a disturbed metabolic environment during pregnancy and lactation have been shown to result in many long-term health consequences for the offspring. Among them, impairments in neurocognitive development and performance belong to the most dreaded ones. So far, very few mechanistic approache...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2017.12.023

    authors: Schmitz L,Kuglin R,Bae-Gartz I,Janoschek R,Appel S,Mesaros A,Jakovcevski I,Vohlen C,Handwerk M,Ensenauer R,Dötsch J,Hucklenbruch-Rother E

    更新日期:2018-03-01 00:00:00

  • Short-term transdermal estradiol therapy, cognition and depressive symptoms in healthy older women. A randomised placebo controlled pilot cross-over study.

    abstract::The potential role of estrogen in protecting women from cognitive decline and reducing depressive symptoms is of great therapeutic interest. In a pilot randomised placebo controlled cross-over study, we aimed to determine the short-term effects of transdermal estradiol therapy on cognition and depressive symptoms in h...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/j.psyneuen.2004.08.007

    authors: Schiff R,Bulpitt CJ,Wesnes KA,Rajkumar C

    更新日期:2005-05-01 00:00:00

  • Androgenic influences on neural asymmetry: Handedness and language lateralization in individuals with congenital adrenal hyperplasia.

    abstract::This study tested the hypothesis that prenatal androgen levels influence hand preferences and language lateralization, two manifestations of neural asymmetry. Participants were individuals with congenital adrenal hyperplasia (CAH, a genetic disorder that results in excess adrenal androgen production beginning prenatal...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章

    doi:10.1016/S0306-4530(03)00145-8

    authors: Mathews GA,Fane BA,Pasterski VL,Conway GS,Brook C,Hines M

    更新日期:2004-07-01 00:00:00

  • Systemic apomorphine alters HPA axis responses to interleukin-1 beta administration but not sound stress.

    abstract::Apomorphine is a dopamine receptor agonist that was recently licensed for the treatment of erectile dysfunction. However, although sexual activity can be stressful, there has been little investigation into whether treatments for erectile dysfunction affect stress responses. We have examined whether a single dose of ap...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/s0306-4530(02)00065-3

    authors: Buller KM,Crane JW,Spencer SJ,Day TA

    更新日期:2003-08-01 00:00:00

  • Mental health and its associations with glucose-lowering medication in women with gestational diabetes mellitus. A prospective clinical cohort study.

    abstract:AIMS:Mental health symptoms are frequent in women with gestational diabetes mellitus (GDM) and may influence glycemic control. We therefore investigated if mental health symptoms (high depression and low well-being scores) predicted a need for glucose-lowering medication and if this use of medication influenced the tra...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2020.105095

    authors: Gilbert L,Nikolaou A,Quansah DY,Rossel JB,Horsch A,Puder JJ

    更新日期:2020-12-01 00:00:00

  • Linking genetic variants of the mineralocorticoid receptor and negative memory bias: interaction with prior life adversity.

    abstract::Substantial research has been conducted investigating the association between life adversity and genetic vulnerability for depression, but clear mechanistic links are rarely identified and investigation often focused on single genetic variants. Complex phenotypes like depression, however, are likely determined by mult...

    journal_title:Psychoneuroendocrinology

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.psyneuen.2013.11.010

    authors: Vogel S,Gerritsen L,van Oostrom I,Arias-Vásquez A,Rijpkema M,Joëls M,Franke B,Tendolkar I,Fernández G

    更新日期:2014-02-01 00:00:00

  • The stress hormone cortisol blocks perceptual learning in humans.

    abstract::Cortisol, the primary glucocorticoid (GC) in humans, influences neuronal excitability and plasticity by acting on mineralocorticoid and glucocorticoid receptors. Cellular studies demonstrated that elevated GC levels affect neuronal plasticity, for example through a reduction of hippocampal long-term potentiation (LTP)...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.psyneuen.2016.12.002

    authors: Dinse HR,Kattenstroth JC,Lenz M,Tegenthoff M,Wolf OT

    更新日期:2017-03-01 00:00:00

  • Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth.

    abstract::The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2018.08.016

    authors: Yirmiya K,Djalovski A,Motsan S,Zagoory-Sharon O,Feldman R

    更新日期:2018-12-01 00:00:00

  • Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans.

    abstract::Pre-clinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2014.12.004

    authors: Bershad AK,Jaffe JH,Childs E,de Wit H

    更新日期:2015-02-01 00:00:00

  • Cortisol, moderated by age, is associated with antidepressant treatment outcome and memory improvement in Major Depressive Disorder: A retrospective analysis.

    abstract:BACKGROUND:Studies testing the relationship between cortisol levels, depression, and antidepressant treatment response have yielded divergent results suggesting the possibility of moderators of a cortisol effect. Several studies indicate that age may moderate the relationship between cortisol and depression. In patient...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2019.104386

    authors: Jain FA,Connolly CG,Reus VI,Meyerhoff DJ,Yang TT,Mellon SH,Mackin S,Hough CM,Morford A,Wolkowitz OM

    更新日期:2019-11-01 00:00:00

  • Pituitary-gonadal function during sleep in healthy aging men.

    abstract::There is limited information on the relation between age-related changes in pituitary-gonadal function and sleep physiology in older men. In this cross-sectional study of 67 healthy volunteers free from sleep complaints, aged 45-75 yr, we (1) assessed peak fluctuations and hourly variations in plasma testosterone, LH ...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/0306-4530(92)90018-3

    authors: Schiavi RC,White D,Mandeli J

    更新日期:1992-11-01 00:00:00

  • Effects of acute and chronic administration of selective monoamine re-uptake inhibitors in the rat forced swim test.

    abstract::The rat forced swim test (FST) is a model that is used extensively as a screening test for antidepressant activity. It has previously been reported that thorough analysis of behaviour in this model reveals two distinct types of active response - climbing and swimming - and that these are separately evoked by re-uptake...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/s0306-4530(02)00026-4

    authors: Kelliher P,Kelly JP,Leonard BE,Sánchez C

    更新日期:2003-04-01 00:00:00

  • How childhood trauma and recent adverse events are related to hair cortisol levels in a large adult cohort.

    abstract:BACKGROUND:Exposure to adversity is a risk factor for many mental and somatic health problems. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is a potential mechanism linking adversity exposure and negative health outcomes. However, associations between adversity exposure and HPA-axis activity have been incons...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2021.105150

    authors: Oresta S,Vinkers CH,van Rossum EFC,Penninx BWJH,Nawijn L

    更新日期:2021-01-20 00:00:00

  • Cortisol modulates men's affiliative responses to acute social stress.

    abstract::The dominant characterization of the physiological and behavioral human stress reaction is the fight-or-flight response. On the other hand, it has been suggested that social affiliation during stressful times ("tend-and-befriend") also represents a common adaptive response to stress, particularly for women. In the cur...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2015.09.004

    authors: Berger J,Heinrichs M,von Dawans B,Way BM,Chen FS

    更新日期:2016-01-01 00:00:00

  • Parental adiposity and cortisol awakening responses in young men and women.

    abstract::A heightened cortisol awakening response (CAR) is associated with adiposity in middle-aged men, but the causal significance of this effect is not known. We hypothesised that if disturbance in cortisol secretion is involved in the development of overweight and obesity, then it might be present in normal weight adults a...

    journal_title:Psychoneuroendocrinology

    pub_type: 杂志文章

    doi:10.1016/j.psyneuen.2006.07.004

    authors: Steptoe A,Wright CE,O'Donnell K,Brydon L,Wardle J

    更新日期:2006-10-01 00:00:00