scholarly journals Networking of glucagon-like peptide-1 axons with GnRH neurons in the basal forebrain of male mice revealed by 3DISCO-based immunocytochemistry and optogenetics

2020 ◽  
Author(s):  
Csaba Vastagh ◽  
Imre Farkas ◽  
Michael M. Scott ◽  
Zsolt Liposits
Keyword(s):  
Basal Forebrain ◽  
Brain Slices ◽  
Low Frequency ◽  
Laser Pulses ◽  
Facilitatory Effect ◽  
Male Mice ◽  
Gnrh Neurons ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Patch Clamp Electrophysiology

Abstract Glucagon-like peptide-1 (GLP-1) regulates reproduction centrally, although, the neuroanatomical basis of the process is unknown. Therefore, the putative networking of the central GLP-1 and gonadotropin-releasing hormone (GnRH) systems was addressed in male mice using whole mount immunocytochemistry and optogenetics. Enhanced antibody penetration and optical clearing procedures applied to 500–1000 µm thick basal forebrain slices allowed the simultaneous visualization of the two distinct systems in the basal forebrain. Beaded GLP-1-IR axons innervated about a quarter of GnRH neurons (23.2 ± 1.4%) forming either single or multiple contacts. GnRH dendrites received a more intense GLP-1 innervation (64.6 ± 0.03%) than perikarya (35.4 ± 0.03%). The physiological significance of the innervation was examined by optogenetic activation of channelrhodopsin-2 (ChR2)-expressing axons of preproglucagon (GCG) neurons upon the firing of GnRH neurons by patch clamp electrophysiology in acute brain slices of triple transgenic mice (Gcg-cre/ChR2/GFP-GnRH). High-frequency laser beam stimulation (20 Hz, 10 ms pulse width, 3 mW laser power) of ChR2-expressing GCG axons in the mPOA increased the firing rate of GnRH neurons (by 75 ± 17.3%, p = 0.0007). Application of the GLP-1 receptor antagonist, Exendin-3-(9-39) (1 μM), prior to the photo-stimulation, abolished the facilitatory effect. In contrast, low-frequency trains of laser pulses (0.2 Hz, 60 pulses) had no effect on the spontaneous postsynaptic currents of GnRH neurons. The findings indicate a direct wiring of GLP-1 neurons with GnRH cells which route is excitatory for the GnRH system. The pathway may relay metabolic signals to GnRH neurons and synchronize metabolism with reproduction.

Toll-like receptor 4 is necessary for glucose-dependent glucagon-like peptide-1 secretion in male mice

2019 ◽  
Vol 510 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Lijuan Wang ◽  
Xiandong Zhan ◽  
Zhenhui Wang ◽  
Jing Ma ◽  
Xiaotong Chang ◽  
...  
Keyword(s):  
Male Mice ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Effect of the Glucagon-like Peptide-1 Receptor (GLP-1R) Agonists on Autonomic Function in Subjects With Diabetes: a Systematic Review and Meta-analysis.

2021 ◽  
Author(s):  
Carla Greco ◽  
Daniele Santi ◽  
Giulia Brigante ◽  
Chiara Pacchioni ◽  
Manuela Simoni
Keyword(s):  
Heart Rate ◽  
Chronic Treatment ◽  
Autonomic Function ◽  
Meta Analysis ◽  
Low Frequency ◽  
Cochrane Collaboration ◽  
Metabolic Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Autonomic Reflex

Abstract Background. In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in people with diabetes remain still debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist chronic treatment on measures of ANS function in people with diabetes. Methods. According to the Cochrane Collaboration and PRISMA statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in people with diabetes chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs). Results. In the studies enrolled, HR significantly increased after treatment (p<0.001), whereas low frequency/high frequency ratio did not differ (p=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (p=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed. Conclusion. The present meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function.

scholarly journals Dendritic Processing of Excitatory Synaptic Input in Hypothalamic Gonadotropin Releasing-Hormone Neurons

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1545-1555 ◽  
Author(s):  
C. B. Roberts ◽  
J. A. Best ◽  
K. J. Suter
Keyword(s):  
Synaptic Input ◽  
Dendritic Structure ◽  
Brain Slices ◽  
Low Frequency ◽  
Reproductive Function ◽  
Synaptic Inputs ◽  
Morphological Findings ◽  
Electrophysiological Recordings ◽  
Excitatory Synaptic Input ◽  
Gnrh Neurons

The activity of hypothalamic GnRH neurons results in the intermittent release of GnRH required for reproductive function. This intermittent neurosecretory activity has been proposed to reflect integration of intrinsic properties of and synaptic input to GnRH neurons. Determining the relative impact of synaptic inputs at different locations on the GnRH neuron is difficult, if not impossible, using only experimental approaches. Thus, we used electrophysiological recordings and neuronal reconstructions to generate computer models of GnRH neurons to examine the effects of synaptic inputs at varying distances from the soma along dendrites. The parameters of the models were adjusted to duplicate measured passive and active electrophysiology of cells from mouse brain slices. Our morphological findings reinforce the emerging picture of a complex dendritic structure of GnRH neurons. Furthermore, analysis of reduced morphology models indicated that this population of cells is unlikely to exhibit low-frequency tonic spiking in the absence of synaptic input. Finally, applying realistic patterns of synaptic input to modeled GnRH neurons indicates that synapses located more than about 30% of the average dendrite length from the soma cannot drive firing at frequencies consistent with neuropeptide release. Thus, processing of synaptic input to dendrites of GnRH neurons is probably more complex than simple summation.

scholarly journals Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4174-4186 ◽  
Author(s):  
Michel K. Herde ◽  
Allan E. Herbison
Keyword(s):  
Action Potential ◽  
Cell Body ◽  
Brain Slices ◽  
Gnrh Neuron ◽  
Male Mice ◽  
Single Action ◽  
Ankyrin G ◽  
Gnrh Neurons ◽  
Action Potential Initiation ◽  
Potential Initiation

GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G–positive axon-like structures. Almost all GnRH neurons (&gt;90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

scholarly journals Glucagon-like peptide 1 receptor-mediated stimulation of a GABAergic projection from the bed nucleus of the stria terminalis to the hypothalamic paraventricular nucleus

2021 ◽  
Author(s):  
Nadya Povysheva ◽  
Huiyuan Zheng ◽  
Linda Rinaman
Keyword(s):  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Brain Slices ◽  
Gabaergic Neurons ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Synaptic Inputs ◽  
Bath Application ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

We previously reported that GABAergic neurons within the ventral anterior lateral bed nucleus of the stria terminalis (alBST) express glucagon-like peptide 1 receptor (GLP1R) in rats, and that virally-mediated <knock-down> of GLP1R expression in the alBST prolongs the hypothalamic-pituitary-adrenal axis response to acute stress. Given other evidence that a GABAergic projection pathway from ventral alBST serves to limit stress-induced activation of the HPA axis, we hypothesized that GLP1 signaling promotes activation of GABAergic ventral alBST neurons that project directly to the paraventricular nucleus of the hypothalamus (PVN). After PVN microinjection of fluorescent retrograde tracer followed by preparation of ex vivo rat brain slices, whole-cell patch clamp recordings were made in identified PVN-projecting neurons within the ventral alBST. Bath application of Exendin-4 (a specific GLP1R agonist) indirectly depolarized PVN-projecting neurons in the ventral alBST and adjacent hypothalamic parastrial nucleus (PS) via circuit-mediated effects that increased excitatory synaptic inputs and decreased inhibitory synaptic inputs to the PVN-projecting neurons; these effects were occluded by prior bath application of a GLP1R antagonist. Additional retrograde tracing experiments combined with in situ hybridization confirmed that PVN-projecting neurons within the ventral alBST/PS are GABAergic, and do not express GLP1R mRNA. Conversely, GLP1 mRNA is expressed by a subset of GABAergic neurons within the oval subnucleus of the dorsal alBST that project into the ventral alBST. Our novel findings reveal a potential GLP1R-mediated mechanism through which the alBST exerts inhibitory control over the endocrine HPA axis.

Effects of glucagon-like peptide-1 (GLP-1) on gastric accommodation, emptying and satiety in humans

2001 ◽  
Vol 120 (5) ◽  
pp. A74-A74
Author(s):  
S AROS ◽  
D KIM ◽  
D BURTON ◽  
G THOMFORDE ◽  
A VELLA ◽  
...  
Keyword(s):  
Gastric Accommodation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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