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Korol, S., Jin, Z. & Birnir, B. (2020). GABA(A) Receptor-Mediated Currents and Hormone mRNAs in Cells Expressing More Than One Hormone Transcript in Intact Human Pancreatic Islets. International Journal of Molecular Sciences, 21(2), Article ID 600.
Open this publication in new window or tab >>GABA(A) Receptor-Mediated Currents and Hormone mRNAs in Cells Expressing More Than One Hormone Transcript in Intact Human Pancreatic Islets
2020 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 21, no 2, article id 600Article in journal (Refereed) Published
Abstract [en]

In pancreatic islets, the major cell-types are alpha, beta and delta cells. The gamma-aminobutyric acid (GABA) signalling system is expressed in human pancreatic islets. In single hormone transcript-expressing cells, we have previously characterized the functional properties of islet GABA(A) receptors (iGABA(A)Rs). Here, we extended these studies to islet cells expressing mRNAs for more than one hormone and sought for correlation between iGABA(A)R activity level and relative mRNA expression ratio. The single-cell RT-PCR in combination with the patch-clamp current recordings was used to examine functional properties of iGABA(A)Rs in the multiple hormone mRNA-expressing cells. We detected cells expressing double (alpha/beta, alpha/delta, beta/delta cell-types) and triple (alpha/beta/delta cell-type) hormone transcripts. The most common mixed-identity cell-type was the alpha/beta group where the cells could be grouped into beta- and alpha-like subgroups. The beta-like cells had low GCG/INS expression ratio (<0.6) and significantly higher frequency of iGABA(A)R single-channel openings than the alpha-like cells where the GCG/INS expression ratio was high (>1.2). The hormone expression levels and iGABA(A)R single-channel characteristics varied in the alpha/beta/delta cell-type. Clearly, multiple hormone transcripts can be expressed in islet cells whereas iGABA(A)R single-channel functional properties appear to be alpha or beta cell specific.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
alpha-like cell, beta cell, GABA, glucagon, insulin, mixed-identity cell
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-407510 (URN)10.3390/ijms21020600 (DOI)000515380000230 ()31963438 (PubMedID)
Funder
Swedish Research Council, 521-2009-4021Swedish Research Council, 521-2012-1789Swedish Research Council, 2015-02417Swedish Diabetes AssociationNovo NordiskSwedish Child Diabetes FoundationErnfors FoundationEXODIAB - Excellence of Diabetes Research in SwedenFredrik och Ingrid Thurings Stiftelse
Available from: 2020-03-26 Created: 2020-03-26 Last updated: 2020-03-26Bibliographically approved
Kvarnung, M., Shahsavani, M., Taylan, F., Moslem, M., Breeuwsma, N., Laan, L., . . . Falk, A. (2019). Ataxia in Patients With Bi-Allelic NFASC Mutations and Absence of Full-Length NF186. Frontiers in Genetics, 10, Article ID 896.
Open this publication in new window or tab >>Ataxia in Patients With Bi-Allelic NFASC Mutations and Absence of Full-Length NF186
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2019 (English)In: Frontiers in Genetics, ISSN 1664-8021, E-ISSN 1664-8021, Vol. 10, article id 896Article in journal (Refereed) Published
Abstract [en]

The etiology of hereditary ataxia syndromes is heterogeneous, and the mechanisms underlying these disorders are often unknown. Here, we utilized exome sequencing in two siblings with progressive ataxia and muscular weakness and identified a novel homozygous splice mutation (c.3020-1G > A) in neurofascin (NFASC). In RNA extracted from fibroblasts, we showed that the mutation resulted in inframe skipping of exon 26, with a deprived expression of the full-length transcript that corresponds to NFASC isoform NF186. To further investigate the disease mechanisms, we reprogrammed fibroblasts from one affected sibling to induced pluripotent stem cells, directed them to neuroepithelial stem cells and finally differentiated to neurons. In early neurogenesis, differentiating cells with selective depletion of the NF186 isoform showed significantly reduced neurite outgrowth as well as fewer emerging neurites. Furthermore, whole-cell patch-clamp recordings of patient-derived neuronal cells revealed a lower threshold for openings, indicating altered Na+ channel kinetics, suggesting a lower threshold for openings as compared to neuronal cells without the NFASC mutation. Taken together, our results suggest that loss of the full-length NFASC isoform NF186 causes perturbed neurogenesis and impaired neuronal biophysical properties resulting in a novel early-onset autosomal recessive ataxia syndrome.

Keywords
neurofascin, neuronal isoform NF186, ataxia, patient-specific induced pluripotent stem cells, neuroepithelial stem cells, neurites
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-395798 (URN)10.3389/fgene.2019.00896 (DOI)000487628800001 ()
Funder
Swedish Research Council, 2015-02424Swedish Research Council, 2017-03407Swedish Research Council, 2017-02936Swedish Foundation for Strategic Research , IB13-0074The Swedish Brain FoundationSwedish Society for Medical Research (SSMF)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-12-09Bibliographically approved
Bhandage, A. K., Cunningham, J. L., Jin, Z., Shen, Q., Bongiovanni, S., Korol, S., . . . Birnir, B. (2019). Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers. International Journal of Molecular Sciences, 20(24), Article ID 6172.
Open this publication in new window or tab >>Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 24, article id 6172Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
GABAA receptor, inflammation, mental health
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-401785 (URN)10.3390/ijms20246172 (DOI)000506840100066 ()31817800 (PubMedID)
Funder
Swedish Research CouncilSwedish Society of Medicine
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2020-03-05Bibliographically approved
Flood, L., Korol, S., Ekselius, L., Birnir, B. & Jin, Z. (2019). Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons. Journal of Neuroimmunology, 337, Article ID UNSP 577050.
Open this publication in new window or tab >>Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons
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2019 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 337, article id UNSP 577050Article in journal (Refereed) Published
Abstract [en]

The neural transmission and plasticity can be differentially modulated by various elements of the immune system. Interferon-gamma (IFN-gamma) is a "pro-inflammatory" cytokine mainly produced by T lymphocytes, activates its corresponding receptor and plays important roles under both homeostatic and inflammatory conditions. However, the impact of IFN-gamma on the gamma-aminobutyric acid (GABA)-mediated currents in the hippocampus, a major brain region involved in the cognitive function, has not been investigated. Here we detected abundant expression of both IFN-gamma receptor subunit gene transcripts (Ifngrl and Ifngr2) in the rat hippocampus by quantitative PCR. In addition, we pre-incubated rat hippocampal slices with IFN-gamma (100 ng/ml) and recorded GABA-activated spontaneous and miniature postsynaptic inhibitory currents (sIPSCs and mIPSCs) and tonic currents in hippocampal CAl pyramidal neurons by the whole-cell patch-clamp method. The pre-incubation with IFN-gamma increased the frequency but not the mean amplitude, rise time or decay time of both sIPSCs and mIPSCs in hippocampal CAl pyramidal neurons, suggesting a presynaptic effect of IFN-gamma. Moreover, the GABA-activated tonic currents were enhanced by IFN-gamma. In conclusion, the potentiation of GABAergic currents in hippocampal neurons by IFN-gamma may contribute to the disturbed neuronal excitability and cognitive dysfunction during neuroinflammation.

Place, publisher, year, edition, pages
ELSEVIER, 2019
Keywords
gamma-Aminobutyric acid, Hippocampus, Interferon-gamma, Phasic inhibition, Tonic inhibition
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-400001 (URN)10.1016/j.jneuroim.2019.577050 (DOI)000498318800004 ()31505410 (PubMedID)
Funder
Swedish Research Council, Dnr 201502417Swedish Research Council, 2018-02952The Swedish Brain Foundation
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2019-12-19Bibliographically approved
Schuster, J., Laan, L., Klar, J., Jin, Z., Huss, M., Korol, S., . . . Dahl, N. (2019). Transcriptomes of Dravet syndrome iPSC derived GABAergic cells reveal dysregulated pathways for chromatin remodeling and neurodevelopment. Neurobiology of Disease, 132, Article ID 104583.
Open this publication in new window or tab >>Transcriptomes of Dravet syndrome iPSC derived GABAergic cells reveal dysregulated pathways for chromatin remodeling and neurodevelopment
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2019 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 132, article id 104583Article in journal (Refereed) Published
Abstract [en]

Dravet syndrome (DS) is an early onset refractory epilepsy typically caused by de novo heterozygous variants in SCN1A encoding the a-subunit of the neuronal sodium channel Na(v)1.1. The syndrome is characterized by age related progression of seizures, cognitive decline and movement disorders. We hypothesized that the distinct neurodevelopmental features in DS are caused by the disruption of molecular pathways in Na(v)1.1 haploinsufficient cells resulting in perturbed neural differentiation and maturation. Here, we established DS-patient and control induced pluripotent stem cell derived neural progenitor cells (iPSC NPC) and GABAergic interneuronal (iPSC GABA) cells. The DS-patient iPSC GABA cells showed a shift in sodium current activation and a perturbed response to induced oxidative stress. Transcriptome analysis revealed specific dysregulations of genes for chromatin structure, mitotic progression, neural plasticity and excitability in DS-patient iPSC NPCs and DS-patient iPSC GABA cells versus controls. The transcription factors FOXM1 and E2F1, positive regulators of the disrupted pathways for histone modification and cell cycle regulation, were markedly up-regulated in DS-iPSC GABA lines. Our study highlights transcriptional changes and disrupted pathways of chromatin remodeling in Na(v)1.1 haploinsufficient GABAergic cells, providing a molecular framework that overlaps with that of neurodevelopmental disorders and other epilepsies.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019
Keywords
Dravet syndrome, SCN1A, Na(v)1.1, iPSC, Neural differentiation, Neurodevelopment, Chromatin architecture
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-398427 (URN)10.1016/j.nbd.2019.104583 (DOI)000497252500015 ()31445158 (PubMedID)
Funder
Swedish Research Council, 2015-02424Swedish Research Council, 2015-02417Knut and Alice Wallenberg FoundationAstraZenecaThe Swedish Brain Foundation, FO2018-0100The Swedish Brain Foundation, FO2019-0210Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

De tre första författarna delar förstaförfattarskapet.

Available from: 2019-12-06 Created: 2019-12-06 Last updated: 2019-12-09Bibliographically approved
Bhandage, A., Jin, Z., Korol, S. V., Tafreshiha, A., Gohel, P., Hellgren, C., . . . Birnir, B. (2018). Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes. PLoS ONE, 13(12), Article ID e0208981.
Open this publication in new window or tab >>Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0208981Article in journal (Refereed) Published
Abstract [en]

Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca-2(+) channels in the plasma membrane are the voltage-gated Ca2+ (Ca-V) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca-V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V)2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca-V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

National Category
Endocrinology and Diabetes Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-372929 (URN)10.1371/journal.pone.0208981 (DOI)000453247500057 ()30543678 (PubMedID)
Funder
Swedish Research CouncilEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Child Diabetes FoundationErnfors Foundation
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
Korol, S. V., Jin, Z., Jin, Y., Bhandage, A. K., Tengholm, A., Gandasi, N. R., . . . Birnir, B. (2018). Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells. EBioMedicine, 30
Open this publication in new window or tab >>Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 30Article in journal (Refereed) Published
Abstract [en]

In human pancreatic islets, the neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule synthesized by and released from the insulin-secreting β cells. The effective, physiological GABA concentration range within human islets is unknown. Here we use native GABAA receptors in human islet β cells as biological sensors and reveal that 100-1000nM GABA elicit the maximal opening frequency of the single-channels. In saturating GABA, the channels desensitized and stopped working. GABA modulated insulin exocytosis and glucose-stimulated insulin secretion. GABAA receptor currents were enhanced by the benzodiazepine diazepam, the anesthetic propofol and the incretin glucagon-like peptide-1 (GLP-1) but not affected by the hypnotic zolpidem. In type 2 diabetes (T2D) islets, single-channel analysis revealed higher GABA affinity of the receptors. The findings reveal unique GABAA receptors signaling in human islets β cells that is GABA concentration-dependent, differentially regulated by drugs, modulates insulin secretion and is altered in T2D.

Keywords
GABA, GABA(A) receptor, Pancreatic islet, Type 2 diabetes
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-348267 (URN)10.1016/j.ebiom.2018.03.014 (DOI)000430303000032 ()29606630 (PubMedID)
Funder
Swedish Research Council, 521-2009-4021EXODIAB - Excellence of Diabetes Research in SwedenSwedish Child Diabetes FoundationSwedish Diabetes AssociationNovo NordiskSwedish Society for Medical Research (SSMF)Swedish Research Council, 521-2012-1789Swedish Research Council, 2015-02417Swedish Research Council, 2017-00956Swedish Research Council, 2014-2575
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-06-19Bibliographically approved
Bhandage, A. K., Jin, Z., Korol, S. V., Shen, Q., Pei, Y., Deng, Q., . . . Birnir, B. (2018). GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes. EBioMedicine, 30, 283-294
Open this publication in new window or tab >>GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 30, p. 283-294Article in journal (Refereed) Published
Abstract [en]

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 (100nM) 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 (100nM, 500nM) 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.

Keywords
PBMCs, Immune cells, Proliferation, Cytokine, GABAA receptor, Diabetes, T1D, Autoimmune disease, T cell
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Research subject
Biology; Physiology
Identifiers
urn:nbn:se:uu:diva-348232 (URN)10.1016/j.ebiom.2018.03.019 (DOI)000430303000033 ()
Funder
Swedish Research Council, 2015-02417Swedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-06-19Bibliographically approved
Korol, S. V., Tafreshiha, A., Bhandage, A. K., Birnir, B. & Jin, Z. (2018). Insulin enhances GABAA receptor-mediated inhibitory currents in rat central amygdala neurons. Neuroscience Letters, 671, 76-81
Open this publication in new window or tab >>Insulin enhances GABAA receptor-mediated inhibitory currents in rat central amygdala neurons
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2018 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 671, p. 76-81Article in journal (Refereed) Published
Abstract [en]

Insulin, a pancreatic hormone, can access the central nervous system, activate insulin receptors distributed in selective brain regions and affect various cellular functions such as neurotransmission. We have previously shown that physiologically relevant concentration of insulin potentiates the GABAA receptor-mediated tonic inhibition and reduces excitability of rat hippocampal CA1 neurons. The central nucleus of the amygdala (CeA) comprises heterogeneous neuronal populations that can respond to hormonal stimulus. Using quantitative PCR and immunofluorescent labeling, we report that the mRNA and protein of the insulin receptor are abundantly expressed in the rat CeA. The insulin receptor mRNA is also detected in the CeA from post-mortem human brain samples. Furthermore, our whole-cell patch-clamp recordings show that the application of insulin (5 and 50 nM) selectively enhances the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat CeA neurons. Our findings reveal that GABAergic synaptic transmission is a target in the CeA for insulin receptor signaling that may underlie insulin modulation of emotion- and feeding-related behaviors.

Keywords
γ-aminobutyric acid, neural inhibition, amygdala, insulin
National Category
Other Biological Topics Biophysics
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-341839 (URN)10.1016/j.neulet.2018.02.022 (DOI)000430523700015 ()29447952 (PubMedID)
Funder
Swedish Research Council, Dnr 2015- 02417The Swedish Brain FoundationÅke Wiberg Foundation, 71959661, M14-0142
Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2018-06-26Bibliographically approved
Bhandage, A. K., Jin, Z., Hellgren, C., Korol, S. V., Nowak, K., Williamsson, L., . . . Birnir, B. (2017). AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women. Journal of Neuroimmunology, 305, 51-58
Open this publication in new window or tab >>AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women
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2017 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 305, p. 51-58Article in journal (Refereed) Published
Abstract [en]

The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-D-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women.

Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and nonpregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluNl, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells.

Keywords
Glutamate, iGluR subunits, Immune cells, Pregnancy, Depression, Physiology-driven changes
National Category
Medical and Health Sciences Neurosciences
Identifiers
urn:nbn:se:uu:diva-282410 (URN)10.1016/j.jneuroim.2017.01.013 (DOI)000397694200009 ()28284346 (PubMedID)
Funder
Swedish Research Council, 521-2012-1789
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2018-01-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4717-1558

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