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Sex Differences in GABAergic Neurotransmission to Gastric‐Projecting DMV Neurons
Author(s) -
Jiang Yanyan,
D'Angelo Michael Paul,
Anselmi Laura,
Travagli R. Alberto
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1254.4
Subject(s) - endocrinology , medicine , estrogen , gabaergic , motility , estrous cycle , antrum , biology , bicuculline , tonic (physiology) , inhibitory postsynaptic potential , stomach , antagonist , receptor , genetics
Functional gastrointestinal disorders, including delayed gastric emptying and decreased gastric motility, are more prevalent in women than men. It is suggested that the abundance of circulating estrogen in women may account for this difference. Gastric motility is finely tuned by the inputs arising from the dorsal motor nucleus of the vagus (DMV), which is itself controlled by a tonic, inhibitory GABAergic input. Estrogen has been shown to increase GABA expression in various CNS area, however the effect of estrogen to modulate GABAergic inputs onto DMV neurons, has not been investigated. The aims of the present study were to test the hypotheses that: i) in female rats the GABAergic tone controlling gastric motility is higher than in male rats; ii) estrogen levels in female rats influence the gastric motility response; and, iii) the response to exogenous application of estrogen in the DMV varies between male and female rats. In vivo anesthetized preparations of Sprague‐Dawley rats were used to compare gastric tone and motility in age‐matched males and virgin females; female rats were further subdivided according to the high estrogen (pro‐estrus and estrus) or low‐estrogen (meta‐ and di‐estrus) period of their cycle. To record gastric tone and motility, miniature strain gauges were sutured onto both the anterior corpus and antrum portions of the stomach. Following exposure of the dorsal brainstem, microinjections of the GABA‐A selective antagonist bicuculline methiodide (BIC, 0.1–5 pmoles/60nL) increased gastric tone and motility in a dose‐dependent manner; the increase was significantly higher in high estrogen (BIC 0.1pmoles increased gastric tone by 192±51 mg and motility by 158±53%; N=5) than in low estrogen females (100±29 mg and 175±112%; N=4) or males (56±17 mg and 111±19%; N=6). Conversely, microinjections of 17b‐estradiol (10pmoles/60nl) decreased gastric motility and tone by −141±26 mg and 145±33% (N=9) in males and by −111±54 mg and 153±40% (N=4) and −205±64 mg and 84±15% (N=5) in low and high‐estrogen females, respectively. The tone and motility effects of 17b‐estradiol were antagonized by pretreatment with the GPER receptor antagonist ICI182,720 (3nmol). The data suggests that i) in female rats the GABAergic tone controlling gastric motility is higher than in male rats; ii) estrogen levels in female rats influence the gastric motility response; and, iii) the response to exogenous application of estrogen in the DMV varies between male and female rats. Taken together, the data supports the hypothesis that estrogen mediates a greater inhibitory input to the DMV through increased expression GABAergic inputs. Support or Funding Information Supported by ANMS and by AHA grants