GLP-1 action in the mouse bed nucleus of the stria terminalis

Autor: Diana L, Williams, Nicole A, Lilly, Ian J, Edwards, Pallas, Yao, James E, Richards, Stefan, Trapp
Rok vydání: 2017
Předmět:
Male
Patch-Clamp Techniques
NTS
nucleus of the solitary tract
BNST
CeA
central amygdaloid nucleus
PB
phosphate buffer
SHi
septohippocampal nucleus
Preproglucagon
Proglucagon
LS
lateral septum
MPA
medial preoptic area
Membrane Potentials
MS
medial septum
Eating
Mice
AAV
adeno-associated virus
HFD
high fat diet
Glucagon-Like Peptide 1
Food intake
NAc
nucleus accumbens
Ex9
exendin (9-39)
digestive
oral
and skin physiology
MeA
medial amygdaloid nucleus
GLP-1
glucagon-like peptide-1
3V
third ventricle
Electrophysiology
GLP-1R
GLP-1 receptor
opt
optic tract
Pir
piriform cortex
VMN
ventromedial nucleus of the hypothalamus
MnPO
median preoptic nucleus
Channelrhodopsin
PPG
Glucagon-like peptide-1 receptor
MM
medial mammillary nucleus
hormones
hormone substitutes
and hormone antagonists
endocrine system
VP
ventral pallidum
Mice
Transgenic
Stress
PPG
preproglucagon
VTA
ventral tegmental area
Article
Quinoxalines
Animals
Arc
arcuate nucleus
ME
median eminence
TTX
tetrodotoxin
BNST
bed nucleus of the stria terminalis
Analysis of Variance
Dose-Response Relationship
Drug
DMH
dorsomedial hypothalamus
Peptide Fragments
Mice
Inbred C57BL
Luminescent Proteins
ACSF
artificial cerebrospinal fluid
LV
lateral ventricle
Septal Nuclei
PFA
paraformaldehyde
Excitatory Amino Acid Antagonists
Stress
Psychological
PVN
paraventricular nucleus
Zdroj: Neuropharmacology
ISSN: 1873-7064
Popis: Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression. The BNST displayed many varicose YFP+ PPG axons in the ventral and less in the dorsal regions. Mice which express RFP in GLP-1R neurons had RFP+ cells throughout the BNST with the highest density in the dorsal part, suggesting that PPG neuron-derived GLP-1 acts in the BNST. Indeed, injection of GLP-1 into the BNST reduced chow intake during the dark phase, whereas injection of the GLP-1 receptor antagonist Ex9 increased feeding. BNST-specific GLP-1-induced food suppression was less effective in mice on high fat (HF, 60%) diet, and Ex9 had no effect. Restraint stress-induced hypophagia was attenuated by BNST Ex9 treatment, further supporting a role for endogenous brain GLP-1. Finally, whole-cell patch clamp recordings of RFP+ BNST neurons demonstrated that GLP-1 elicited either a depolarizing or hyperpolarizing reversible response that was of opposite polarity to that under dopamine. Our data support a physiological role for BNST GLP-1R in feeding, and suggest complex cellular responses to GLP-1 in this nucleus.
Graphical abstract Image 1
Highlights • NTS PPG neurons project strongly to the BNST. • Exogenous or endogenous GLP-1 acting in the BNST potently reduces food intake. • Stress-induced hypophagia is attenuated by GLP-1 receptor blockade in the BNST. • Within the BNST, GLP-1 elicits both excitatory and inhibitory electrical responses. • GLP-1 likely acts on both orexigenic and anorexigenic efferent pathways from the BNST.
Databáze: OpenAIRE
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