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Babateen, Omar
Alternative names
Publications (7 of 7) Show all publications
Babateen, O., Korol, S. V., Jin, Z., Bhandage, A. K., Ahemaiti, A. & Birnir, B. (2017). Liraglutide modulates GABAergic signaling in rat hippocampal CA3 pyramidal neurons predominantly by presynaptic mechanism. BMC Pharmacology & Toxicology, 18, Article ID 83.
Open this publication in new window or tab >>Liraglutide modulates GABAergic signaling in rat hippocampal CA3 pyramidal neurons predominantly by presynaptic mechanism
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2017 (English)In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 18, article id 83Article in journal (Refereed) Published
Abstract [en]

Background

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain where it regulates activity of neuronal networks. The receptor for glucagon-like peptide-1 (GLP-1) is expressed in the hippocampus, which is the center for memory and learning. In this study we examined effects of liraglutide, a GLP-1 analog, on GABA signaling in CA3 hippocampal pyramidal neurons.

Methods

We used patch-clamp electrophysiology to record synaptic and tonic GABA-activated currents in CA3 pyramidal neurons in rat hippocampal brain slices.

Results

We examined the effects of liraglutide on the neurons at concentrations ranging from one nM to one μM. Significant changes of the spontaneous inhibitory postsynaptic currents (sIPSCs) were only recorded with 100 nM liraglutide and then in just ≈50% of the neurons tested at this concentration. In neurons affected by liraglutide both the sIPSC frequency and the most probable amplitudes increased. When the action potential firing was inhibited by tetrodotoxin (TTX) the frequency and amplitude of IPSCs in TTX and in TTX plus 100 nM liraglutide were similar.

Conclusions

The results demonstrate that liraglutide regulation of GABA signaling of CA3 pyramidal neurons is predominantly presynaptic and more limited than has been observed for GLP-1 and exendin-4 in hippocampal neurons.

Keywords
GABA, GLP-1 receptor, patch-clamp, inhibitory postsynaptic and tonic currents, hippocampus, electrophysiology
National Category
Other Biological Topics Neurosciences Pharmacology and Toxicology
Research subject
Neuroscience; Pharmacology; Biology with specialization in Molecular Biology
Identifiers
urn:nbn:se:uu:diva-282424 (URN)10.1186/s40360-017-0191-0 (DOI)000418264400001 ()29246184 (PubMedID)
Projects
Effect of metabolic hormones on GABA signalling in the hippocampus
Funder
Swedish Research CouncilThe Swedish Brain FoundationEXODIAB - Excellence of Diabetes Research in SwedenÅke Wiberg Foundation
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2018-02-16Bibliographically approved
Babateen, O. M. (2016). GABA signaling regulation by GLP-1 receptor agonists and GABA-A receptors modulator. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>GABA signaling regulation by GLP-1 receptor agonists and GABA-A receptors modulator
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

GABA (γ-aminobutyric acid) is the main neuroinhibitory transmitter in mammalian brains.  It binds to GABA-A and GABA-B receptors. The GABA-A receptors are ligand-gated chloride channels. A variety of GABA-A receptor agonists and antagonists have been developed to study the GABA-mediated inhibition and to explore new medications. In this thesis I have examined the role of GABA in brain tumors and the effects of the metabolic hormone GLP-1 on GABAergic signaling in neurons.

I studied if GABA-A receptors subunits were expressed and formed functional ion channels in the glioblastoma cell line U3047MG. I identified the mRNA of 11, α2, α3, α5, β1, β2, β3, δ, γ3, π, θ and ρ2, out of the 19 known GABA-A subunits. Immunostaining demonstrated abundant expression of the α3 and β3 subunits. Interestingly, whole-cell GABA-activated currents were recorded in only 12% of the cells. The GABA-activated currents half-maximal concentration (EC50) was 36 µM. The currents were modulated by diazepam (1 µM) and the general anesthetics propofol (50 µM) and etomidate (EC50 = 50 nM).

GLP-1 and exendin-4 transiently enhanced the GABA-A receptor-mediated currents in CA3 neurons of the rat hippocampus. The tonic and the spontaneous inhibitory postsynaptic currents increased as compared to control in a concentration dependent manner.  The increase was related to enhanced release of GABA from the presynaptic terminals and increased insertion or affinity of GABA-A receptors in the CA3 postsynaptic neuron. In contrast to GLP-1 and exendin-4, liraglutide enhanced the currents only in a subset of the neurons and the effect was mainly mediated by presynaptic mechanisms. 

In conclusion, GABA signaling in neurons is modified by the metabolic hormone GLP-1 and its mimetics highlighting the important cross-talk that takes place between the brain and other organs. Medicines modifying GABA signaling in the brain may be important for a number of diseases.  

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. p. 51
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1209
National Category
Medical and Health Sciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-282431 (URN)978-91-554-9548-0 (ISBN)
Public defence
2016-05-31, C2:301, BMC, Husargatan 3, 751 24, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2016-05-02 Created: 2016-04-05 Last updated: 2016-05-12
Babateen, O., Jin, Z., Bhandage, A. K., Korol, S. V., Westermark, B., Forsberg Nilsson, K., . . . Birnir, B. (2015). Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from Human glioblastoma. European Journal of Pharmacology, 748, 101-107
Open this publication in new window or tab >>Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from Human glioblastoma
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2015 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 748, p. 101-107Article in journal (Refereed) Published
Abstract [en]

GABAA receptors are pentameric chloride ion channels that are opened by GABA. We have screened a cell line derived from human glioblastoma, U3047MG, for expression of GABAA receptor subunit isoforms and formation of functional ion channels. We identified GABAA receptors subunit α2, α3, α5, β1, β2, β3, δ, γ3, π, and θ mRNAs in the U3047MG cell line. Whole-cell GABA-activated currents were recorded and the half-maximal concentration (EC50) for the GABA-activated current was 36μM. The currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and enhanced by the benzodiazepine diazepam (1μM) and the general anesthetics etomidate and propofol (50μM). In line with the expressed GABAA receptors containing at least the α3β3θ subunits, the receptors were highly sensitive to etomidate (EC50=55nM). Immunocytochemistry identified expression of the α3 and β3 subunit proteins. Our results show that the GABAA receptors in the glial cell line are functional and are modulated by classical GABAA receptor drugs. We propose that the U3047MG cell line may be used as a model system to study GABAA receptors function and pharmacology in glial cells.

National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-239191 (URN)10.1016/j.ejphar.2014.12.001 (DOI)000348840500013 ()25510230 (PubMedID)
Available from: 2014-12-19 Created: 2014-12-19 Last updated: 2018-01-11
Korol, S. V., Jin, Z., Babateen, O. & Birnir, B. (2015). GLP-1 and Exendin-4 Transiently Enhance GABA(A) Receptor-Mediated Synaptic and Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons. Diabetes, 64(1), 79-89
Open this publication in new window or tab >>GLP-1 and Exendin-4 Transiently Enhance GABA(A) Receptor-Mediated Synaptic and Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons
2015 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, no 1, p. 79-89Article in journal (Refereed) Published
Abstract [en]

GLP-1 is a hormone that stimulates insulin secretion. Receptors for GLP-1 are also found in the brain, including the hippocampus, the centre for memory and learning. Diabetes mellitus is a risk factor for decreased memory functions. We studied effects of GLP-1 and exendin-4, a GLP-1 receptor agonist, on γ-aminobutyric acid (GABA) signaling in hippocampal CA3 pyramidal neurons. GABA is the main inhibitory neurotransmitter and decreases neuronal excitability. GLP-1 (0.01 – 1 nmol/L) transiently enhanced synaptic and tonic currents and the effects were blocked by exendin(9–39). Ten pmol/L GLP-1 increased both the spontaneous inhibitory postsynaptic current (sIPSC) amplitudes and frequency by a factor of 1.8. In 0.1, 1 nmol/L GLP-1 or 10, 50 or 100 nmol/L exendin-4, only the sIPSC frequency increased. The tonic current was enhanced by 0.01 – 1 nmol/L GLP-1 and by 0.5 – 100 nmol/L exendin-4. When action potentials were inhibited by tetrodotoxin (TTX), IPSCs decreased and currents were no longer potentiated by GLP-1 or exendin-4. In contrast, although the tonic current decreased in TTX, it was still enhanced by GLP-1 or exendin-4. The results demonstrate GLP-1 receptor regulation of hippocampal function and are consistent with GLP-1 receptor agonists enhancing GABAA signaling by pre- and postsynaptic mechanisms.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-234954 (URN)10.2337/db14-0668 (DOI)000346765600010 ()
Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-12-05Bibliographically approved
Korol, S. V., Jin, Z., Babateen, O. & Birnir, B. (2015). Modulation of GABAA receptor-mediated synaptic and tonic currents in the rat hippocampus by GLP-1, exendin-4 and diazepam. Acta Physiologica, 215, 89-90
Open this publication in new window or tab >>Modulation of GABAA receptor-mediated synaptic and tonic currents in the rat hippocampus by GLP-1, exendin-4 and diazepam
2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, p. 89-90Article in journal, Meeting abstract (Other academic) Published
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-284884 (URN)000370526500124 ()
Available from: 2016-04-19 Created: 2016-04-19 Last updated: 2018-01-10Bibliographically approved
Babateen, O. M., Jin, Z., Bhandage, A. K., Korol, S. V., Westermark, B., Nilsson, K. F., . . . Birnir, B. (2014). GABA-A receptor currents in a cell line (U3047MG) derived from a human glioblastoma tumor are enhanced by etomidate, propofol and diazepam. Paper presented at Scandinavian Physiological Society's Annual Meeting, 22–24 August 2014, Stockholm, Sweden. Acta Physiologica, 211(S696), 100-100, Article ID P74.
Open this publication in new window or tab >>GABA-A receptor currents in a cell line (U3047MG) derived from a human glioblastoma tumor are enhanced by etomidate, propofol and diazepam
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2014 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, no S696, p. 100-100, article id P74Article in journal, Meeting abstract (Other academic) Published
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-247720 (URN)000349466000164 ()
Conference
Scandinavian Physiological Society's Annual Meeting, 22–24 August 2014, Stockholm, Sweden
Available from: 2015-03-24 Created: 2015-03-23 Last updated: 2018-01-11
Korol, S. V., Jin, Z., Babateen, O. M. & Birnir, B. (2014). GABA(A) receptor-mediated currents in the hippocampus are transiently enhanced by glucagon-like peptide-1 receptor (GLP-1R) agonists. Paper presented at Scandinavian Physiological Society's Annual Meeting, 22–24 August 2014, Stockholm, Sweden. Acta Physiologica, 211(S696), 83-83, Article ID P38.
Open this publication in new window or tab >>GABA(A) receptor-mediated currents in the hippocampus are transiently enhanced by glucagon-like peptide-1 receptor (GLP-1R) agonists
2014 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, no S696, p. 83-83, article id P38Article in journal, Meeting abstract (Other academic) Published
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-247717 (URN)000349466000129 ()
Conference
Scandinavian Physiological Society's Annual Meeting, 22–24 August 2014, Stockholm, Sweden
Available from: 2015-03-24 Created: 2015-03-23 Last updated: 2018-01-11Bibliographically approved
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