The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons

Korol, Sergiy V.; Jin, Zhe; Birnir, Bryndis

doi:10.1371/journal.pone.0124765

Cited by 22 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, LDTg GABA neurons may potentially be the target of GLP-1RA exendin-4's pharmacological action in cocaine (Hernandez et al, 2020). Consistent with these results, the patch-clamp recordings found that GLP-1 and exendin-4 temporarily regulated synaptic and tonic currents activated by GABA in CA3 pyramidal neurons, and thereby augmenting GABA signaling in CA3 Pyramidal Neurons (Jin et al, 2015;Babateen et al, 2017;Korol et al, 2015). Overall, the translational implications of these findings indicate an essential yet largely unexplored effects of GLP-1RAs on LDTg GABA neurons and a novel neurobiological mechanism by which GLP-1RAs attenuate cocaine-seeking and reinstatement.…”

Section: Glutamate Mechanismsupporting

confidence: 69%

Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder

Zhu

Kong

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Cocaine use disorder (CUD) is a major public health challenge with a high relapse rate and lack of effective pharmacotherapies; therefore, there is a substantial need to identify novel medications to treat this epidemic. Since the advent of glucagon-like peptide-1 (GLP-1) receptors (GLP-1Rs) agonists (GLP-1RAs), their potential has been extensively explored and expanded. In this review, we first summarized the biological effects of GLP-1, GLP-1Rs, and GLP-1RAs. Subsequently, the recent literature examining the behavioral effects and the possible pharmacological mechanisms of GLP-1RAs on CUD was reviewed. Increasing preclinical evidence suggests that GLP-1RAs are promising in regulating dopamine release, dopamine transporter (DAT) surface expression and function, mesolimbic reward system and GABAergic neurons, and maladaptive behaviors in animal models of self-administration and conditioned place preference. In addition, the emerging role of GLP-1RAs in inhibiting inflammatory cytokines was reported. These findings indicate that GLP-1RAs perform essential functions in the modulation of cocaine-seeking and cocaine-taking behaviors likely through multifaceted mechanisms. Although the current preclinical evidence provides convincing evidence to support GLP-1RA as a promising pharmacotherapy for CUD, other questions concerning clinical availability, impact and specific mechanisms remain to be addressed in further studies.

show abstract

Section: Glutamate Mechanismsupporting

confidence: 69%

Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder

Zhu

Kong

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Similarly, GABA A receptor-mediated spontaneous inhibitory postsynaptic current in hippocampal CA3 pyramidal neurons are increased by GLP-1 and exendin-4 in an exendin 3 (9-39)-and TTX-sensitive manner [44,45]. Again, these results indicate that GLP-1R activation can evoke GABA release from presynaptic elements.…”

Section: Figmentioning

confidence: 71%

Presynaptic GLP‐1 receptors enhance the depolarization‐evoked release of glutamate and GABA in the mouse cortex and hippocampus

et al. 2017

View full text Add to dashboard Cite

Glucagon-like peptide-1 receptors (GLP-1Rs) have been shown to mediate cognitive-enhancing and neuroprotective effects in the central nervous system. However, little is known about their physiological roles on central neurotransmission, especially at the presynaptic level. Using purified synaptosomal preparations and immunofluorescence techniques, here we show for the first time that GLP-1Rs are localized on mouse cortical and hippocampal synaptic boutons, in particular on glutamatergic and GABAergic nerve terminals. Their activation by the selective agonist exendin-4 (1-100 nM) was able to increase the release of either [ H]d-aspartate or [ H]GABA. These effects were abolished by 10 nM of the selective GLP1-R antagonist exendin-3 (9-39) and were prevented by the selective adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (10 µM), indicating the involvement of classic GLP-1Rs coupled to G protein stimulating cAMP synthesis. Our data demonstrate the existence and activity of presynaptic receptors for GLP-1 that could represent additional mechanisms by which this neurohormone exerts its effects in the CNS. © 2017 BioFactors, 44(2):148-157, 2018.

show abstract

“…GLP-1, an incretin, is not only secreted from intestinal L cells, but also is expressed in neurons of the central nervous system 43 . Many studies have revealed that GLP-1 32 , 44 , EX-4 45 - 47 , and other agonists of GLP-1R 40 , 48 have a neuroprotective role against neurodegenerative cell death, traumatic brain injury, and ischemic stroke. Previous reports indicate that the neuroprotective effects of GLP-1 and EX-4 involve reducing infarct size and stoke volume 28 , 32 as well as anti-apoptotic effects 28 , 39 .…”

Section: Discussionmentioning

confidence: 99%

Activation of GLP-1 Receptor Enhances Neuronal Base Excision Repair via PI3K-AKT-Induced Expression of Apurinic/Apyrimidinic Endonuclease 1

Yang

Chen

et al. 2016

Theranostics

View full text Add to dashboard Cite

Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage. We show that activation of GLP-1 receptor (GLP-1R) protect cortical neurons from menadione induced oxidative DNA damage via a signaling pathway involving enhanced DNA repair. GLP-1 stimulates DNA repair by activating the cyclic AMP response element binding protein (CREB) which, consequently, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair (BER) pathway. In this study, APE1 expression was down-regulated as a consequence phosphatidylinositol-3 kinase (PI3K) suppression by the inhibitor LY294002, but not by the suppression of MEK activity. Ischemic stroke is typically caused by overwhelming oxidative-stress in brain cells. Administration of exentin-4, an analogue of GLP-1, efficiently enhanced DNA repair in brain cells of ischemic stroke rats. Our study suggests that a new function of GLP-1 is to elevate DNA repair by inducing the expression of the DNA repair protein APE1.

show abstract

The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons

Cited by 22 publications

References 35 publications

Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder

Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder

Presynaptic GLP‐1 receptors enhance the depolarization‐evoked release of glutamate and GABA in the mouse cortex and hippocampus

Activation of GLP-1 Receptor Enhances Neuronal Base Excision Repair via PI3K-AKT-Induced Expression of Apurinic/Apyrimidinic Endonuclease 1

Contact Info

Product

Resources

About