Asymmetric effects of low doses of progesterone on GABA(A) receptor α4 subunit protein expression in the olfactory bulb of female rats

Arbo, Bruno Dutra; Andrade, Sabrina Chapuis de; Osterkamp, Gabriela; Gomez, Rosane; Ribeiro, Maria Flávia Marques

doi:10.1139/cjpp-2014-0307

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…Unlike estrogen, there are not extensive data documenting the specific neural systems regulated by progesterone, so it is difficult to propose neurobiological pathways. However, promising data suggest that progesterone may play an important regulatory role in gene expression within several systems (e.g., serotonin, Gamma-Amino Butyric acid) that are thought to be important in anxiety and/or depression (Arbo, Andrade, Osterkamp, Gomez, & Ribeiro, 2014; Bethea & Centeno, 2008; Bethea & Reddy, 2015; Lu, Eshleman, Janowsky, & Bethea, 2003; Quast et al, 2014; Schüle, Nothdurfterb, & Rupprecht, 2014). It is likely that progesterone activates genetic effects via the same mechanisms as those proposed for estrogen during puberty (e.g., differential production of neurotransmitters and/or their receptors), although this possibility awaits investigation.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

Klump

O'Connor

Hildebrandt

et al. 2016

Clinical Psychological Science

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Recent data show shifts in genetic and environmental influences on emotional eating across the menstrual cycle, with significant shared environmental influences during pre-ovulation, and primarily genetic effects during post-ovulation. Factors driving differential effects are unknown, although increased estradiol during pre-ovulation and increased progesterone during post-ovulation are thought to play a role. We indirectly investigated this possibility by examining whether overall levels of estradiol and progesterone differentially impact genetic and environmental risk for emotional eating in adult female twins (N = 571) drawn from the MSU Twin Registry. Emotional eating, estradiol levels, and progesterone levels were assessed daily and then averaged to create aggregate measures for analysis. As predicted, shared environmental influences were significantly greater in twins with high estradiol levels, whereas additive genetic effects increased substantially across low versus high progesterone groups. Results highlight significant and differential effects of ovarian hormones on etiologic risk for emotional eating in adulthood.

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Section: Discussionmentioning

confidence: 99%

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

Klump

O'Connor

Hildebrandt

et al. 2016

Clinical Psychological Science

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“…[62] In addition, PROG concentration decreases in female patients with menstrual anxiety, with PROG acting directly on GABA A R or exerting an antianxiety effect by affecting ALLO production. [63][64][65] Studies have confirmed that Gelsemium alkaloids can promote neuroactive steroid synthesis, mainly reflected in upregulated 3α-HSOR gene expression by gelsemine and koumine and TSPO activation by koumine. [34,57] Neuroactive steroids can regulate GlyR and GABA A R activity, causing chloride ion influx, hyperpolarization of the related neuronal cell membrane, and reduced postsynaptic potential, resulting in anxiolytic, sedative, and analgesic effects.…”

Section: Glyr/3α-hsor/allo/gaba a R/hpa Axis Pathwaymentioning

confidence: 95%

“…It also enhanced GABA A R activity in mice, producing anxiolytic effects [62] . In addition, PROG concentration decreases in female patients with menstrual anxiety, with PROG acting directly on GABA A R or exerting an antianxiety effect by affecting ALLO production [63‐65] . Studies have confirmed that Gelsemium alkaloids can promote neuroactive steroid synthesis, mainly reflected in upregulated 3α‐HSOR gene expression by gelsemine and koumine and TSPO activation by koumine [34,57] .…”

Section: Antianxiety‐related Mechanismsmentioning

confidence: 98%

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

Long,

Tang,

Zuo

et al. 2023

Brain-X

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The genus Gelsemium belongs to the family Loganiaceae, one of the traditional Chinese herbs. Gelsemium is traditionally used to treat rheumatoid and neuropathic pain. Its root extracts were found to protect against anxiety, especially the alkaloids koumine and gelsemine. Indeed, koumine and gelsemine can act as positive agonists of the glycine receptor (GlyR), which reduces neuronal excitability through chloride influx and can also increase neuroactive steroid content by enhancing 3alpha‐hydroxysteroid oxidoreductase (3α‐HSOR) expression. The latter can activate the excitation‐inhibitory response via the γ‐aminobutyric acid type A receptor (GABAAR), reduce the abnormal corticotropin‐releasing hormone (CRH) increase in the hypothalamus, inhibit adrenocorticotropic hormone (ACTH) secretion, and effectively inhibit the abnormal ACTH and corticosterone increases in the circulation. In addition, koumine and gelsemine inhibited the expression of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, inhibiting the release of inflammatory factors and regulating anxiety‐related neural circuits. Gelsemine also inhibited the overexpression of brain‐derived neurotrophic factor (BDNF) and cAMP response element‐binding protein (CREB) in the hypothalamus to maintain the plasticity of brain neurons and protect neurogenesis to achieve anxiety regulation. In general, this article reviews the recent studies on Gelsemium in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of Gelsemium as a therapeutic drug for anxiety‐related diseases.

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“…Steroid hormones are neuromodulators of GABAA receptors (Gunn et al, 2015) and were shown to activate GABAergic neurons in the lateral septal nucleus in ovariectomized rats (Briski & Singh, 2008). Progesterone produces time-dependent anxiolytic-like effects that have been attributed to both non-genomic factors [e.g., direct or indirect modulation of GABAA receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors (Barth, Villringer, & Sacher, 2015) and monoamine release (Tonge & Greengrass, 1971)], and genomic factors (e.g., higher expression of GABAA receptor subunits; Nin et al, 2008;Arbo, Andrade, Osterkamp, Gomez, & Ribeiro, 2014). In the brain, progesterone produces direct or indirect effects.…”

Section: Introductionmentioning

confidence: 99%

Actions of progesterone on depression-like behavior in a model of surgical menopause are mediated by GABAA receptors

et al. 2020

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Introduction. In rats, long-term ovariectomy results in low concentrations of steroid hormones and reproduces anxiety- and depression-like behavior after surgical menopause in women. Progesterone produces antidepressant-like effects two weeks post-ovariectomy (i.e., early post-ovariectomy) through actions on γ-aminobutyric acid-A (GABAA) receptors, but its antidepressant-like effects and mechanism of action in rats eight weeks post-ovariectomy (i.e., late post-ovariectomy, considered a model of surgical menopause) remain unknown. Objective. To explore the antidepressant-like effects of progesterone and the participation of GABAA receptors in rats eight weeks post-ovariectomy. Method. Long-term ovariectomized female Wistar rats were treated sub-acutely with vehicle or progesterone (.5, 1, and 2 mg/kg) and subjected to the open field and forced swim tests, and behavior was compared with cycling or fluoxetine-treated rats. The rats were then pretreated with picrotoxin (1 mg/kg) followed by progesterone (1 mg/kg) to explore the role of GABAA receptors in long-term-induced depression-like behavior. Results. Long-term ovariectomized rats exhibited depression-like behavior in the forced swim test compared with intact rats, an effect that was not observed in progesterone- and fluoxetine-treated long-term ovariectomized rats. These effects were not attributable to psychomotor alterations. In the open field test, the time spent rearing and grooming was lower in ovariectomized rats compared with intact rats, which was not observed in progesterone- and fluoxetine-treated rats. Picrotoxin blocked the effects of progesterone in both behavioral tests. Discussion and conclusion. These results indicated that sub-acute progesterone treatment reduced depression-like behavior through actions on GABAA receptors in a rat model of surgical menopause.

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Asymmetric effects of low doses of progesterone on GABA(A) receptor α4 subunit protein expression in the olfactory bulb of female rats

Cited by 5 publications

References 21 publications

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

Actions of progesterone on depression-like behavior in a model of surgical menopause are mediated by GABAA receptors

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