Testing the critical window of estradiol replacement on gene expression of vasopressin, oxytocin, and their receptors, in the hypothalamus of aging female rats

Garcia, Alexandra N.; Depena, Christina; Yin, Wang; Gore, Andrea C.

doi:10.1016/j.mce.2015.10.004

Cited by 9 publications

(13 citation statements)

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“…After reproductive senescence, there could be an adjustment in estrogen receptor sensitivity [ 44 , 45 , 46 ] that affects the critical period for an intervention with estrogens. Importantly, most studies perform OVX before periestropause and evaluate the critical window for intervention considering the period of estrogen decline [ 12 , 33 , 45 , 47 ], but not the age at which OVX is performed. In this sense, recently García et al [ 47 ] showed that changes in the expression of genes involved in social and affiliative behaviors—such as vasopressin and oxitocin—varied according to the age when OVX was performed as well as the interval after OVX.…”

Section: Discussionmentioning

confidence: 99%

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The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

et al. 2016

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The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE2) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE2 (1.25, 2.5 or 5.0 µg/rat, s.c.; −48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE2 (1.25 µg/rat, s.c., −48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE2 administration. EE2 (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE2 (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE2 was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE2 alone or in combination with CIT.

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Section: Discussionmentioning

confidence: 99%

“…The drugs were freshly prepared. The doses and latencies were chosen from previous studies [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ].…”

Section: Methodsmentioning

confidence: 99%

The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

et al. 2016

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“…Tissue samples assayed in this study were previously generated and utilized for separate publications ( 15 , 16 ). This study utilized the cDNA generated by these previous publications.…”

Section: Methodsmentioning

confidence: 99%

“…Utilizing a reproductive aging female rat model ( 15 , 16 ), we sought to determine the impact of age and hormone treatment duration and timing on genes crucial for GnRH-(1–5) signaling, particularly in the medial preoptic area (mPOA) and arcuate nucleus (ARC) of the hypothalamus. The mPOA is of interest as GnRH cell bodies are mainly found here, and it is a major site for the regulation of reproductive function ( 17 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Gonadotropin-Releasing Hormone-(1–5) Signaling Genes by Estradiol Is Age Dependent

et al. 2017

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Gonadotropin-releasing hormone (GnRH) is a key regulatory molecule of the hypothalamus–pituitary (PIT)–gonadal (HPG) axis that ultimately leads to the downstream release of estradiol (E2) and progesterone (P). These gonadal steroids feed back to the hypothalamus and PIT to regulate reproductive function and behavior. While GnRH is thought to be the master regulator of reproduction, its metabolic product GnRH-(1–5) is also biologically active. Thimet oligopeptidase 1 (also known as EP24.15) cleaves GnRH to form GnRH-(1–5). GnRH-(1–5) is involved in regulation of the HPG axis, exerting its actions through a pair of orphan G protein-coupled receptors, GPR101 and GPR173. The physiological importance of GnRH-(1–5) signaling has been studied in several contexts, but its potential role during reproductive senescence is poorly understood. We used an ovariectomized (OVX) rat model of reproductive senescence to assess whether and how GnRH-(1–5) signaling genes in hypothalamic subnuclei change in response to aging and/or different estradiol replacement regimens designed to model clinical hormone replacement in women. We found that Gpr101 and Gpr173 mRNA expression was increased with age in the arcuate nucleus, while expression of Gpr173 and EP24.15 increased with age in the medial preoptic area. Treatment with E2 in younger OVX animals increased expression of Gpr101, Gpr173, and EP24.15. However, older animals treated with E2 showed decreased expression of these GnRH-(1–5) signaling genes, displaying an age-related decline in responsiveness to E2. To our knowledge, this is the first study to systematically assess the effects of age and different clinically relevant regimens of E2 replacement on GnRH-(1–5) signaling genes.

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“…The prefrontal cortex (PFC), medial amygdala (MeA), bed nucleus of the stria terminalis (BNST) and the hypothalamus are among the estrogen-sensitive nodes of this neural circuit (Arimatsu and Hatanaka, 1986; Kugaya et al, 2003; Han and De Vries, 2003; Garcia et al, 2016). Considering their key roles and abundant expression of ERs (Kugaya et al, 2003; Walker et al, 2003; Saper et al, 2005), they are important targets of analysis for understanding potential neuromolecular substrates involved in estrogens’ regulation of social behavior.…”

Section: Introductionmentioning

confidence: 99%

The effects of long-term estradiol treatment on social behavior and gene expression in adult female rats

Garcia

Bezner

Depena

et al. 2017

Hormones and Behavior

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This study tested the effects of long-term estradiol (E2) replacement on social behavior and gene expression in brain nuclei involved in the regulation of these social behaviors in adult female rats. We developed an ultrasonic vocalization (USV) test and a sociability test to examine communications, social interactions, and social preference, using young adult female cagemates. All rats were ovariectomized (OVX) and implanted with a Silastic capsule containing E2 or vehicle, and housed in same-treatment pairs for a 3-month period. Then, rats were behaviorally tested, euthanized, and 5 nuclei in the brain’s social decision-making circuit were selected for neuromolecular profiling by a multiplex qPCR method. Our novel USV test proved to be a robust tool to measure numbers and types of calls emitted by cagemates that had been reintroduced after a 1-week separation. Results also showed that E2-treated OVX rats had profoundly decreased numbers of USV calls compared to vehicle-treated OVX rats. In a test of sociability, in which a female was allowed to choose between her cagemate or a same-treatment novel rat, we found few effects of E2 compared to vehicle, although interestingly, rats chose the cagemate over an unfamiliar conspecific. Gene expression results revealed that the supraoptic nucleus had the greatest number of gene changes caused by E2: Oxt, Oxtr and Avp were increased, and Drd2, Htr1a, Grin2b, and Gabbr1 were decreased, by E2. No genes were affected in the prefrontal cortex, and 1–4 genes were changed in paraventricular nucleus (Pgr), bed nucleus of the stria terminalis (Oxtr, Esr2, Dnmt3a), and medial amygdala (Oxtr, Ar, Foxp1, Tac3). Thus, E2 changes communicative interactions between adult female rats, together with selected expression of genes in the brain, especially in the supraoptic nucleus.

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Testing the critical window of estradiol replacement on gene expression of vasopressin, oxytocin, and their receptors, in the hypothalamus of aging female rats

Cited by 9 publications

References 82 publications

The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

Regulation of Gonadotropin-Releasing Hormone-(1–5) Signaling Genes by Estradiol Is Age Dependent

The effects of long-term estradiol treatment on social behavior and gene expression in adult female rats

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