Tamoxifen Mimics the Effects of Endogenous Ovarian Hormones on Repeated Seizures Induced by Pentylenetetrazole in Rats

Mansouri, Somaeh; Ataei, Mariam Lale; Hosseini, Mahmoud; Bideskan, Ali Reza Ebrahimzadeh

doi:10.5607/en.2013.22.2.116

Cited by 12 publications

(10 citation statements)

References 58 publications

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“… 38 , 39 , 40 It has been shown that seizures may lead to morphological changes such as production of dark neurons, in brain tissue. 10 , 32 Dark neurons, previously were considered as histological artifacts in neurosurgical biopsies 34 , 41 but later, they were seen after brain trauma. 34 , 42 Recently, it has been well documented that dark neurons are also produced without any trauma or mechanical forces.…”

Section: Discussionmentioning

confidence: 99%

The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats

Seghatoleslam

Alipour

Shafieian

et al. 2016

Journal of Traditional and Complementary Medicine

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Nigella sativa (NS) has been suggested to have neuroprotective and anti-seizures properties. The aim of current study was to investigate the effects of NS hydro-alcoholic extract on neural damage after pentylenetetrazole (PTZ) – induced repeated seizures. The rats were divided into five groups: (1) control (saline), (2) PTZ (50 mg/kg, i.p.), (3–5) PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 (100, 200 and 400 mg/kg of NS extract respectively, 30 min prior to each PTZ injection on 5 consecutive days). The passive avoidance (PA) test was done and the brains were then removed for histological measurements. The PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 groups had lower seizure scores than PTZ group (P < 0.01 and P < 0.001). The latency to enter the dark compartment by the animals of PTZ group was lower than control in PA test (P < 0.01). Pre-treatment by 400 mg/kg of the extract increased the latency to enter the dark compartment (P < 0.05). Meanwhile, different doses of the extract inhibited production of dark neurons in different regions of hippocampus (P < 0.001). The present study allows us to suggest that the NS possesses a potential ability to prevent hippocampal neural damage which is accompanied with improving effects on memory.

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Section: Discussionmentioning

confidence: 99%

The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats

Seghatoleslam

Alipour

Shafieian

et al. 2016

Journal of Traditional and Complementary Medicine

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“…These compounds have been shown to exert estrogen-like neuroprotective actions in the brain. Tamoxifen, one of SERMs, is extensively used in breast cancer 6 . In CNS, tamoxifen has both agonistic and antagonsistic effects on estrogen receptors 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Tamoxifen, one of SERMs, is extensively used in breast cancer 6 . In CNS, tamoxifen has both agonistic and antagonsistic effects on estrogen receptors 6 . There is also evidence that SERMs may affect mood, depression and anxiety 7 .…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

Azizi-Malekabadi

Pourganji

Zabihi

et al. 2015

Arq. Neuro-Psiquiatr.

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The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.Keywords: rat, ovariectomized, tamoxifen, depression, forced swimming test, open field, elevated plus maze. RESUMOForam investigados os efeitos do tamoxifeno (TAM) no comportamento semelhante a ansiedade de depressão de ratas ooforectomizadas (OVX) e controles. Os animais foram divididos em Sham-TAM, OVX-TAM, Sham e OVX groups. Tamoxifeno (1 mg/kg) foi administrado por quatro semanas. No teste de natação forçada, os tempos de imobilidade nos grupos OVX e Sham-TAM foram maiores que aqueles do grupo Sham. No campo aberto, os números de cruzamento no centro nos grupos OVX e Sham-TAM foram menores que aquele do grupo Sham, e o número dos cruzamentos na periferia no grupo OVX foi menor que o número no grupo Sham. No labirinto elevado, os números de entradas com braços abertos entre os animais nos grupos Sham-TAM e OVX foram menores do que aqueles do grupo Sham, enquanto o número de entradas com os braços abertos no grupo OVX-TAM foi maior que aquele no grupo OVX. Foi observado que a deleção dos hormônios ovarianos induziu comportamento similar a ansiedade e depressão. A administração de tamoxifeno em ratos controle induziu a um comportamento que era comparável aos efeitos da deleção do hormônio ovariano. Pode ser sugerido que o tamoxifeno antagoniza os efeitos dos hormônios ovarianos. Parece também que o tamoxifeno tem efeito ansiolítico nas ratas ooforectomizadas.Palavras-chave: rato, ooforectomia, tamoxifeno, depressão, teste de natação forçada, campo aberto, labirinto elevado.

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“…injected for 28 days. The doses of the treatments were based on previous studies reporting the antioxidant actions of the agents (Kumral et al, 2014;Reddy, 2009;Zheng et al, 2004;Wang et al, 2013;Gómez et al, 2009;Mansouri et al, 2013). Following the 28-day treatment period, epileptic seizure was induced by a single-dose of PTZ (45 mg kg −1 ), while the tap water-given control group was injected with saline.…”

Section: Methodsmentioning

confidence: 99%

Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure

Koyuncuoğlu

Tamer

Erzik

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?Could different hormonally active substances, including oestrogen receptor (ER) agonists, protect against oxidative brain damage and memory impairment induced by a single epileptic seizure in rats? If so, which signalling mechanisms are involved in their anti‐inflammatory effects? What is the main finding and its importance?Chronic administration of oestrogen, progesterone, ER modulators/agonists or blockade of testosterone exhibited anti‐inflammatory and antioxidant actions on single seizure‐induced neuronal injury, while ER agonists additionally improved memory function and up‐regulated CREB signalling and hippocampal GABA(A)α1 receptor density, suggesting that ERα or ERβ receptor activation may be beneficial in protecting against seizure‐related oxidative brain injury and cognitive dysfunction. Abstract The susceptibility to epileptic seizures is dependent on sex as well as fluctuations in oestrogen levels, while exogenous oestrogen was shown to have no effect or to facilitate or to inhibit seizure activity. Oestrogen receptors (ERs) mediate antioxidant and anti‐inflammatory actions in several inflammatory models, but the involvement of ERs in seizure‐induced neuronal injury has not been evaluated previously. In order to assess the effects of resveratrol, progesterone, oestradiol (E2), an anti‐testosterone (cyproterone acetate; CPA), a selective ER modulator (tamoxifen; TMX) and ERα/ERβ agonists (propyl pyrazole triol (PPT), diarylpropionitrile (DPN)) on oxidative brain damage and memory impairment due to epileptic seizure, male Wistar rats (n = 120) received one of the treatment choices either in drinking water or intraperitoneally for 31 days, and epileptic seizure was induced on the 28th day by injection of a single‐dose of pentylenetetrazole (45 mg kg−1). The results demonstrate that chronic pretreatment with resveratrol, progesterone, E2, CPA or TMX suppressed most of the inflammatory parameters indicative of oxidative neuronal injury, while treatment with the ER agonists DPN or PPT were found to be even more effective in limiting the oxidative damage. Treatment with DPN resulted in the up‐regulation of cAMP response element‐binding protein (CREB) and brain‐derived neurotrophic factor (BDNF) expression, while PPT up‐regulated expression of CREB without affecting BDNF levels. Moreover, both ER agonists provided protection against seizure‐induced memory loss with a concomitant increase in hippocampal GABA(A)α1‐positive cells. In conclusion, ER agonists, and more specifically ERβ agonist, appear to provide maximum protection against seizure‐induced oxidative brain injury and associated memory dysfunction by up‐regulating the expression of CREB, BDNF and GABA(A)α1 receptors.

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Tamoxifen Mimics the Effects of Endogenous Ovarian Hormones on Repeated Seizures Induced by Pentylenetetrazole in Rats

Cited by 12 publications

References 58 publications

The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats

The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure

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