Expression of <scp>GABA</scp> receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health

Bhandage, Amol K.; Hellgren, Charlotte; Jin, Zhe; Ólafsson, Einar B.; Sundström‐Poromaa, Inger; Birnir, Bryndis

doi:10.1111/apha.12440

Cited by 31 publications

(37 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The alteration in the chloride gradient across the plasma membrane is potentially partially compensated for by the somewhat increased GABA concentration in the plasma. A similar down-regulation of NKCC1 has been observed in cells from both healthy and depressed pregnant women [28] and from T1D patients [7]. This observation indicates a general shift of immune regulation by altered GABA signaling, rather than a decrease specifically associated with depression.…”

Section: Immunomodulation By Gabasupporting

confidence: 71%

“…Plasma and PBMCs were isolated from freshly drawn blood samples, as previously described [28]. The plasma was isolated by centrifugation at 3600 rpm for 10 min at 4 • C and immediately frozen at −80 • C. PBMCs were prepared by first diluting the blood samples in an equal volume of MACS buffer (Miltenyi Biotec, Madrid, Spain), and layered on Ficoll-paque plus (Sigma-Aldrich, Hamburg, Germany).…”

Section: Plasma and Pbmc Isolation From Blood Samplesmentioning

confidence: 99%

“…A recently identified drainage system of the brain, the glymphatic system, indicates that the brain is a significant source of the GABA present in blood [27]. The expression of GABA receptor subunits and activation of functional GABA A receptors have been recorded in immune cells such as peripheral blood mononuclear cells (PBMCs), T cells, monocytes, dendritic cells, and macrophages [7,28]. Recently, we demonstrated that GABA inhibits the secretion of a variety of inflammatory protein markers from PBMCs and T cells from healthy individuals and type 1 diabetes patients [7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers

Bhandage

Cunningham

Jin

et al. 2019

IJMS

View full text Add to dashboard Cite

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers. Thirteen of these markers displayed augmented levels in patients compared to CBD. Twenty-one markers correlated with the age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients, as was the average plasma GABA concentration. GABA modulated the release of seven cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) from the patients. The study reveals significant changes in the plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.

show abstract

Section: Immunomodulation By Gabasupporting

confidence: 71%

Section: Plasma and Pbmc Isolation From Blood Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers

Bhandage

Cunningham

Jin

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Where GABA in blood comes from is still being explored, but the recently discovered drainage system of the brain, the glymphatic system ( Plog and Nedergaard, 2018 ), identifies the brain, in addition to peripheral organs, as a potential source for GABA in blood. In the pancreatic islets, GABA is an auto- and paracrine signaling molecule activating GABA receptors on the endocrine cells and, perhaps, also on immune cells that may enter the islets ( Birnir and Korpi, 2007 ; Kanaani et al, 2015 ; Caicedo, 2013 ; Bhandage et al, 2015 ). Similarly, in blood, immune cells may be regulated by GABA ( Bhandage et al, 2015 ; Bjurstom et al, 2008 ; Tian et al, 2004 ; Tian et al, 1999 ).…”

Section: Introductionmentioning

confidence: 99%

“…In the pancreatic islets, GABA is an auto- and paracrine signaling molecule activating GABA receptors on the endocrine cells and, perhaps, also on immune cells that may enter the islets ( Birnir and Korpi, 2007 ; Kanaani et al, 2015 ; Caicedo, 2013 ; Bhandage et al, 2015 ). Similarly, in blood, immune cells may be regulated by GABA ( Bhandage et al, 2015 ; Bjurstom et al, 2008 ; Tian et al, 2004 ; Tian et al, 1999 ). In T1D, the β cell mass declines and, thereby, also the local source for GABA in the pancreatic islets ( Fiorina, 2013 , Tian et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes

et al. 2018

View full text Add to dashboard Cite

The neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule in the brain and in pancreatic islets. Here, we demonstrate that GABA regulates cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. In anti-CD3 stimulated PBMCs, GABA (100 nM) inhibited release of 47 cytokines in cells from patients with type 1 diabetes (T1D), but only 16 cytokines in cells from nondiabetic (ND) individuals. CD4+ T cells from ND individuals were grouped into responder or non-responder T cells according to effects of GABA (100 nM, 500 nM) on the cell proliferation. In the responder T cells, GABA decreased proliferation, and inhibited secretion of 37 cytokines in a concentration-dependent manner. In the non-responder T cells, GABA modulated release of 8 cytokines. GABA concentrations in plasma from T1D patients and ND individuals were correlated with 10 cytokines where 7 were increased in plasma of T1D patients. GABA inhibited secretion of 5 of these cytokines from both T1D PBMCs and ND responder T cells. The results identify GABA as a potent regulator of both Th1- and Th2-type cytokine secretion from human PBMCs and CD4+ T cells where GABA generally decreases the secretion.

show abstract

GABAergic signaling in human and murine NK cells upon challenge withToxoplasma gondii

Bhandage

Friedrich

Kanatani

et al. 2021

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Protective cytotoxic and proinflammatory cytokine responses by NK cells impact the outcome of infections by Toxoplasma gondii, a common parasite in humans and other vertebrates. However, T. gondii can also sequester within NK cells and downmodulate their effector functions. Recently, the implication of GABA signaling in infection and inflammation-related responses of mononuclear phagocytes and T cells has become evident. Yet, the role of GABAergic signaling in NK cells has remained unknown. Here, we report that human and murine NK cells synthesize and secrete GABA in response to infection challenge. Parasitized NK cells secreted GABA, whereas activation stimuli, such as IL-12/IL-18 or parasite lysates, failed to induce GABA secretion. GABA secretion by NK cells was associated to a transcriptional up-regulation of GABA synthesis enzymes (glutamate decarboxylases [GAD65/67]) and was abrogated by GAD inhibition. Further, NK cells expressed GABA-A receptor subunits and GABA signaling regulators, with transcriptional modulations taking place upon challenge with T. gondii. Exogenous GABA and GABA-containing supernatants from parasitized dendritic cells (DCs) impacted NK cell function by reducing the degranulation and cytotoxicity of NK cells. Conversely, GABA-containing supernatants from NK cells enhanced the migratory responses of parasitized DCs. This enhanced DC migration was abolished by GABA-A receptor antagonism or GAD inhibition and was reconstituted by exogenous GABA. Jointly, the data show that NK cells are GABAergic cells and that GABA hampers NK cell cytotoxicity in vitro. We hypothesize that GABA secreted by parasitized immune cells modulates the immune responses to T. gondii infection.

show abstract

Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health

Abstract: The results demonstrate the impact gender, pregnancy and mental health have on the expression of GABA receptors and chloride transporters expressed in human PBMCs.

Cited by 31 publications

References 42 publications

Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers

Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers

GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes

GABAergic signaling in human and murine NK cells upon challenge withToxoplasma gondii

Contact Info

Product

Resources

About