Journal article
Perinatal high-fat diet alters development of GABA A receptor subunits in dorsal motor nucleus of vagus
American journal of physiology: Gastrointestinal and liver physiology, v 317(1), pp G40-G50
01 Jul 2019
PMID: 31042399
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Perinatal high-fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABA
receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic
(E13) to postnatal
(P42), and response to brainstem microinjection of benzodiazepines was assessed. Whole cell patch clamp recordings from DMV neurons assessed the functional expression of GABA
α subunits, whereas mRNA and protein expression were measured via qPCR and Western blotting, respectively. pHFD decreased basal antrum and corpus motility, whereas brainstem microinjection of L838,417 (positive allosteric modulator of α
subunit-containing GABA
receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABA
α
and
subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABA
α
receptor subunits on DMV neurons and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABA
α
subunit-containing receptors implies that such developmental changes may contribute to the observed decreased gastric motility.
Vagal neurocircuits involved in the control of gastric functions, satiation, and food intake are subject to significant developmental regulation postnatally, with immature GABA
receptors expressing slower α
-subunits, whereas mature GABA
receptor express faster α
-subunits. After perinatal high-fat diet exposure, this developmental regulation of dorsal motor nucleus of the vagus (DMV) neurons is disrupted, increasing their tonic GABAergic inhibition, decreasing efferent output, and potentially decreasing gastric motility.
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Details
- Title
- Perinatal high-fat diet alters development of GABA A receptor subunits in dorsal motor nucleus of vagus
- Creators
- Courtney Clyburn - Penn State Milton S. Hershey Medical CenterCaitlin A Howe - Penn State Milton S. Hershey Medical CenterAmy C Arnold - Penn State Milton S. Hershey Medical CenterCharles H Lang - Penn State Milton S. Hershey Medical CenterR Alberto Travagli - Penn State Milton S. Hershey Medical CenterKirsteen N Browning - Penn State Milton S. Hershey Medical Center
- Publication Details
- American journal of physiology: Gastrointestinal and liver physiology, v 317(1), pp G40-G50
- Publisher
- American Physiological Society (APS)
- Grant note
- TL1 TR002016 / NCATS NIH HHS F31 DK118833 / NIDDK NIH HHS UL1 TR002014 / NCATS NIH HHS R01 DK099350 / NIDDK NIH HHS R01 DK111667 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000474866500004
- Scopus ID
- 2-s2.0-85069265166
- Other Identifier
- 991022008195604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Gastroenterology & Hepatology
- Physiology