Differential role of estrogen receptor modulators in depression-like behavior and memory impairment in rats with postmenopausal diabetes

Bansal, Seema; Chopra, Kanwaljit

doi:10.1097/gme.0000000000000435

Cited by 18 publications

(10 citation statements)

References 51 publications

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“…Furthermore, the antidepressant effects of estradiol on serotonergic neurotransmission and depressive behavior appear to be mediated preferentially via ERβ. For example, selective agonists for ERβ, but not ERα, produced antidepressant effects, such as decreased immobility and increased struggling and swimming in the forced swim test in rats ( Walf et al, 2004 ; Rocha et al, 2005 ; Clark et al, 2012 ; Bansal and Chopra, 2015 ; Bastos et al, 2015 ; Benmansour et al, 2016 ). In addition, the antidepressant activity of estradiol has been shown to be absent in knockout mice for ERβ ( Rocha et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, considering the normal or high levels of estradiol during perimenopause, the use of extra doses of estrogen to ameliorate mood disorders in perimenopausal women is counterintuitive. Thus, to clarify this question, we raise three possibilities: (1) estradiol can increase the expression of PRs ( MacLusky and McEwen, 1978 ; Helena et al, 2009 ), thus, it is reasonable to suggest that estrogen therapy, by increasing PR expression, compensates for the low plasma levels of progesterone; (2) as estrogen effects on mood predominately occur through ERβ ( Bansal and Chopra, 2015 ; Bastos et al, 2015 ; Benmansour et al, 2016 ), estradiol therapy during perimenopause may positively modulate ERβ expression; and (3) because estrogens increases the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis ( Hiroi et al, 2006 ), it may rectify potential deviations in serotonin synthesis in the dorsal raphe nucleus (DRN), a central nucleus for the control of emotions. To test these hypotheses, we used an animal model of perimenopause in which the natural follicle depletion is accelerated by the 4-vinylcycloxene diepoxide (VCD) retaining residual ovarian tissue ( Lohff et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD)

Pestana-Oliveira

Kalil

Leite

et al. 2018

eNeuro

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Chronic exposure to 4-vinylcycloxene diepoxide (VCD) in rodents accelerates the natural process of ovarian follicular atresia modelling perimenopause in women. We investigated why estrogen therapy is beneficial for symptomatic women despite normal or high estrogen levels during perimenopause. Female rats (28 d) were injected daily with VCD or oil for 15 d; 55-65 d after the first injection, pellets of 17β-estradiol or oil were inserted subcutaneously. Around 20 d after, the rats were euthanized (control rats on diestrus and estradiol-treated 21 d after pellets implants). Blood was collected for hormone measurement, the brains were removed and dorsal raphe nucleus (DRN), hippocampus (HPC), and amygdala (AMY) punched out for serotonin (5-HT), estrogen receptor β (ERβ), and progesterone receptor (PR) mRNA level measurements. Another set of rats was perfused for tryptophan hydroxylase (TPH) immunohistochemistry in the DRN. Periestropausal rats exhibited estradiol levels similar to controls and a lower progesterone level, which was restored by estradiol. The DRN of periestropausal rats exhibited lower expression of PR and ERβ mRNA and a lower number of TPH cells. Estradiol restored the ERβ mRNA levels and number of serotonergic cells in the DRN caudal subregion. The 5-HT levels were lower in the AMY and HPC in peristropausal rats, and estradiol treatment increased the 5-HT levels in the HPC and also increased ERβ expression in this area. In conclusion, estradiol may improve perimenopause symptoms by increasing progesterone and boosting serotonin pathway from the caudal DRN to the dorsal HPC potentially through an increment in ERβ expression in the DRN.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD)

Pestana-Oliveira

Kalil

Leite

et al. 2018

eNeuro

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“…Seven studies focused on depression-like behaviour [6,11,[48][49][50][51][52]. The first [48] described that activation of ERβ in the CA3 region of hippocampus induced by DPN slowed serotonin clearance via MAPK/ERK1/2 signaling and interactions with both TrKB and IGF-1 receptors whereas no role of PI3K/Akt signaling in mediating this effect was shown.…”

Section: Psychological and Psychiatric Outcomesmentioning

confidence: 98%

“…These results show an antidepressant-like effect of ERβ agonist. Moreover, the other six studies used the widely used behavioural assays/tests, Porsolt test or forced swim test and found an anti-depressant effect of ERβ activation [6,11,[49][50][51][52].…”

Section: Psychological and Psychiatric Outcomesmentioning

confidence: 99%

The functions of estrogen receptor beta in the female brain: A systematic review

et al. 2016

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“…ER receptors are located in cells in both cytoplasm and nucleus. Their location is not permanent, but the process is rather dynamica result of translocation from and to the cell nucleus [25,26]. Both ERα and ERβ regulate the synthesis and metabolism of many neurotransmitters and neuropeptides, their receptors, and transporters, and also play a role in non-genomic cell signalling (the so-called rapid mechanism of action) [3,27].…”

Section: Introductionmentioning

confidence: 99%

Expression of ESR1 and ESR2 oestrogen receptor encoding gene and personality traits – preliminary study

Talarowska

Szemraj

2019

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Introduction: The main objective of the study is to examine the hypothesis claiming a correlation between personality traits measured with the use of the Minnesota Multiphasic Personality Inventory (MMPI-2) personality questionnaire and the expression of the ERα (ESR1) and ERβ (ESR2) encoding gene in patients suffering from depression. Material and methods: The experiment was carried out on a group of 44 individuals with depression. The Polish variant of the MMPI-2 was applied with the aim of assessing personality traits. Furthermore, the authors evaluated the expression of the genes encoding the oestrogen receptors (ERα and ERβ) at the mRNA level and protein level in the studied population. Results: No significant differences in the expression of ERα and ERβ encoding genes were found and confirmed in the patients with the first episode of depression and those suffering from subsequent episodes of the disease. No differences were found between women and men, either. In women a positive relationship was found between the scale of psychopathy (p = 0.04), paranoia (p = 0.01), and mania (p = 0.03) and expression for the ERα encoding gene at the mRNA level. A negative relationship was found between the mania scale and ERβ encoding gene expression at mRNA (p = 0.03) and protein (p = 0.04) levels. In males a positive relationship between anxiety as a personality trait and expression of the ERβ receptor encoding gene at mRNA level (p = 0.03) and protein level (p = 0.03) was found. Conclusions: Personality traits may be linked with the expression of genes encoding oestrogen receptors (ERα and ERβ) among patients with depressive disorders.

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Differential role of estrogen receptor modulators in depression-like behavior and memory impairment in rats with postmenopausal diabetes

Abstract: Results reveal that specific ER-β agonists can ameliorate memory dysfunction and depressive behavior associated with postmenopausal diabetes and are devoid of the feminizing adverse effects of nonselective ER agonists.

Cited by 18 publications

References 51 publications

Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD)

Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD)

The functions of estrogen receptor beta in the female brain: A systematic review

Expression of ESR1 and ESR2 oestrogen receptor encoding gene and personality traits – preliminary study

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