Effect of tibolone on dendritic spine density in the rat hippocampus

Beltrán-Campos, Vicente; Dı́az-Ruiz, Araceli; Padilla-Gómez, E.; Zavala, Herlinda Aguilar; Rı́os, Camilo; Cintra, Sofía Díaz

doi:10.1016/j.nrleng.2014.03.004

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…In addition to some reports suggesting that tibolone may improve semantic memory and cognition in postmenopausal women [3][4][5][6], neuroprotective actions of the steroid have been reported in different animal and cellular models. Thus, tibolone improves cognition deficits and decreases CA1 dendritic spine pruning caused by ovariectomy in female rats [7,8] and in male rats exposed to ozone improves memory and protects the hippocampus from oxidative stress and cholinergic alterations [9,10].…”

Section: Introductionmentioning

confidence: 99%

The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge

Crespo‐Castrillo

Garcia-Segura

Arévalo

2020

J Neuroinflammation

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Background: Tibolone is a synthetic steroid used in clinical practice for the treatment of climacteric symptoms and osteoporosis. Active metabolites of tibolone, generated in target tissues, have an affinity for estrogen and androgen receptors. Astrocytes are direct targets for estrogenic compounds and previous studies have shown that tibolone protects brain cortical neurons in association with a reduction in reactive astrogliosis in a mouse model of traumatic brain injury. Since phagocytosis is a crucial component of the neuroprotective function exerted by astrocytes, in the present study, we have assessed whether tibolone regulates phagocytosis in primary astrocytes incubated with brain-derived cellular debris. Methods: Male and female astrocyte cell cultures were obtained from newborn (P0-P2) female and male Wistar rats. Astrocytic phagocytosis was first characterized using carboxylate beads, Escherichia coli particles, or brain-derived cellular debris. Then, the effect of tibolone on the phagocytosis of Cy3-conjugated cellular debris was quantified by measuring the intensity of Cy3 dye-emitted fluorescence in a given GFAP immunoreactive area. Before the phagocytosis assays, astrocytes were incubated with tibolone in the presence or absence of estrogen or androgen receptor antagonists or an inhibitor of the enzyme that synthesizes estradiol. The effect of tibolone on phagocytosis was analyzed under basal conditions and after inflammatory stimulation with lipopolysaccharide. Results: Tibolone stimulated phagocytosis of brain-derived cellular debris by male and female astrocytes, with the effect being more pronounced in females. The effect of tibolone in female astrocytes was blocked by a selective estrogen receptor β antagonist and by an androgen receptor antagonist. None of these antagonists affected tibolone-induced phagocytosis in male astrocytes. In addition, the inhibition of estradiol synthesis in the cultures enhanced the stimulatory effect of tibolone on phagocytosis in male astrocytes but blocked the effect of the steroid in female cells under basal conditions. However, after inflammatory stimulation, the inhibition of estradiol synthesis highly potentiated the stimulation of phagocytosis by tibolone, particularly in female astrocytes. Conclusions: Tibolone exerts sex-specific regulation of phagocytosis in astrocytes of both sexes, both under basal conditions and after inflammatory stimulation.

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Section: Introductionmentioning

confidence: 99%

The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge

Crespo‐Castrillo

Garcia-Segura

Arévalo

2020

J Neuroinflammation

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“…Although tibolone is one of the main drugs used for the treatment of postmenopausal symptoms, there is limited information on its effects in the brain. Nevertheless, it is known that tibolone has effects on the nervous system, since it reverses the loss of dendritic spines caused by ovariectomy in rat CA1 hippocampal pyramidal cells [31]. The steroid has also rapid effects in the activity of pro-opiomelanocortin (POMC) hypothalamic neurons, acting on membrane estrogen receptors [32].…”

Section: Introductionmentioning

confidence: 99%

The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury

et al. 2018

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Previous studies have shown that estradiol reduces reactive gliosis after a stab wound injury in the cerebral cortex. Since the therapeutic use of estradiol is limited by its peripheral hormonal effects, it is of interest to determine whether synthetic estrogenic compounds with tissue-specific actions regulate reactive gliosis. Tibolone is a synthetic steroid that is widely used for the treatment of climacteric symptoms and/or the prevention of osteoporosis. In this study, we have assessed the effect of tibolone on reactive gliosis in the cerebral cortex after a stab wound brain injury in ovariectomized adult female mice. By 7 days after brain injury, tibolone reduced the number of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the number of microglial cells with a reactive phenotype in comparison to vehicle-injected animals. These effects on gliosis were associated with a reduction in neuronal loss in the proximity to the wound, suggesting that tibolone exerts beneficial homeostatic actions in the cerebral cortex after an acute brain injury.

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“…Other studies demonstrated the protective effect of tibolone against lipid peroxidation and protein oxidation [195]. Tibolone is capable of increasing the density of dendritic spines in hippocampal neurons, indicating a potential role in synaptic plasticity and memory [196]. Guzmán et al (2007), also showed that tibolone metabolites exert estrogenic activity on human astrocytes and oligodendrocyteslike cell lines [187].…”

Section: Selective Tissue Estrogenic Activity Regulatorsmentioning

confidence: 97%

Neuroactive Steroids in Hypoxic–Ischemic Brain Injury: Overview and Future Directions

Toro-Urrego¹,

Ávila-Rodriguez²,

Herrera³

et al. 2020

Neuroprotection - New Approaches and Prospects

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Hypoxic–ischemic brain injury is a number one cause of long-term neurologic disability and death worldwide. This public health burden is mainly characterized by a decrease in oxygen concentration and blood flow to the tissues, which lead to an inefficient supply of nutrients to the brain. This condition induces cell death by energy depletion and increases free radical generation and inflammation. Hypoxic–ischemic brain injury may occur in ischemic-stroke and over perinatal asphyxia, being both leading causes of morbidity in adults and children, respectively. Currently, there are no effective pharmaceutical strategies to prevent the triggering of secondary injury cascades, including oxidative stress and metabolic dysfunction. Neuroactive steroids like selective estrogen receptor modulators, SERMs, and selective tissue estrogenic activity regulators, STEARs, exert several neuroprotective effects. These encompass mitochondrial survival, a decrease in reactive oxygen species, and maintenance of cell viability, among others. In this context, these neurosteroids constitute promising molecules, which could modify brain response to injury. Here we show an updated overview of the underlying mechanisms of hypoxic–ischemic brain injury. We also highlight the neuroprotective effects of neurosteroids and their future directions.

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Effect of tibolone on dendritic spine density in the rat hippocampus

Cited by 8 publications

References 19 publications

The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge

The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge

The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury

Neuroactive Steroids in Hypoxic–Ischemic Brain Injury: Overview and Future Directions

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