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Perinatal high-fat diet alters development of GABAA receptor subunits in dorsal motor nucleus of vagus.
Clyburn, Courtney; Howe, Caitlin A; Arnold, Amy C; Lang, Charles H; Travagli, R Alberto; Browning, Kirsteen N.
Afiliação
  • Clyburn C; Department of Neural and Behavioral Sciences, Penn State College of Medicine , Hershey, Pennsylvania.
  • Howe CA; Department of Neural and Behavioral Sciences, Penn State College of Medicine , Hershey, Pennsylvania.
  • Arnold AC; Department of Neural and Behavioral Sciences, Penn State College of Medicine , Hershey, Pennsylvania.
  • Lang CH; Department of Cellular and Molecular Physiology, Penn State College of Medicine , Hershey, Pennsylvania.
  • Travagli RA; Department of Neural and Behavioral Sciences, Penn State College of Medicine , Hershey, Pennsylvania.
  • Browning KN; Department of Neural and Behavioral Sciences, Penn State College of Medicine , Hershey, Pennsylvania.
Am J Physiol Gastrointest Liver Physiol ; 317(1): G40-G50, 2019 07 01.
Article em En | MEDLINE | ID: mdl-31042399
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 GABAA 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 day 13 (E13) to postnatal day 42 (P42), and response to brainstem microinjection of benzodiazepines was assessed. Whole cell patch clamp recordings from DMV neurons assessed the functional expression of GABAA 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 α2/3 subunit-containing GABAA 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 GABAA α1,2, and 3 subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABAA α2/3 receptor subunits on DMV neurons and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA α2/3 subunit-containing receptors implies that such developmental changes may contribute to the observed decreased gastric motility. NEW & NOTEWORTHY Vagal neurocircuits involved in the control of gastric functions, satiation, and food intake are subject to significant developmental regulation postnatally, with immature GABAA receptors expressing slower α2/3-subunits, whereas mature GABAA receptor express faster α1-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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Estômago / Nervo Vago / Tronco Encefálico / Receptores de GABA-A / Dieta Hiperlipídica / Motilidade Gastrointestinal Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Estômago / Nervo Vago / Tronco Encefálico / Receptores de GABA-A / Dieta Hiperlipídica / Motilidade Gastrointestinal Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2019 Tipo de documento: Article