Cognitive effects of long-term dydrogesterone treatment used alone or with estrogen on rat menopausal models of different ages

Liu, J.; Lin, Haiqing; Huang, Yanhong; Liu, Y.; Wang, B.; Su, Fan

doi:10.1016/j.neuroscience.2015.01.042

Cited by 15 publications

(8 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, cognitive deficits are more pronounced when ovaries removal is practiced at young age, which is consistent with clinical findings showing that cognitive decline coincides with surgical menopause at earlier ages (Liu et al 2015;Shuster et al 2010;Bove et al 2014;Rocca and Henderson 2014). Thus the cognitive decline appears as an issue of aging associated with gonadal steroid deficiency.…”

Section: Discussionsupporting

confidence: 86%

“…In this sense, an amount of studies have shown that hippocampus-dependent learning and memory are impaired by OVX (Su et al 2011;Cai et al 2013;Qu et al 2013). For instance, OVX rats (10-11 months old), tested in the Morris water maze, display impaired spatial learning if compared to their intact counterparts (Liu et al 2015), and OVX mice, tested in the Y-maze, display lower correct rates than sham animals (Cai et al 2013). Similarly, memory deficits (evaluated in either the water maze and the Y-maze) produced by the i.c.v.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1

et al. 2016

View full text Add to dashboard Cite

One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15 months after the ovaries removal. In these animals, ovariectomy was performed at 3 months of age. These data were compared with those derived from intact rats at 8, 13 and 18 months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Similar results were reported in a recent study that examined E2 ± dydrogesterone (DG) using a similar method of hormone administration. Histological analysis of mammary glands revealed that DG did not reverse the atrophic morphology observed in OVX rats, however, treatment with E2 with or without DG resulted in mammary glands similar to those of sham controls [30]. While the measurement included here was a qualitative overview of mammary gland morphology, these results are interesting as previous research has indicated that E2 is required for pubertal mammary gland development but P4 is also required for mammary gland maintenance during adulthood in mice [31].…”

Section: Discussionmentioning

confidence: 99%

Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary Tumorigenesis in Ovariectomized Rats without Progesterone

et al. 2016

View full text Add to dashboard Cite

A role for estrogens in breast cancer is widely accepted, however, recent evidence highlights that timing and exposure levels are important in determining whether they elicit harmful versus beneficial effects. The rat chemical carcinogen model has been widely used to study the effects of estrogens but conclusions on the levels that lead to tumor development and an absolute requirement for progesterone (P4) are lacking. A newer method of hormone administration mixes hormones with nut butter for peroral consumption allowing for a less stressful method of long-term administration with lower spikes in serum estradiol (E2) levels. The present study was designed to determine if estrogens alone at a physiological dose can drive carcinogen-induced tumors in ovariectomized (OVX) rats or if P4 is also required using this method of hormone administration. Short-term studies were conducted to determine the dose of estrogen (E) that would lead to increased uterine weight following OVX. Subsequently, rats were OVX on postnatal day (PND) 40 then treated daily with E (600 μg/kg/day), P4 (15 mg/kg/day), or the combination. On PND 50, all rats were injected with nitrosomethylurea to induce mammary tumors. Uterine weights, body weights, and serum E2 levels were measured to demonstrate the efficacy of the method for increasing E2 levels during long-term treatment. After 26 weeks, tumor incidence was similar in Sham, E, and E + P4 animals indicating that E was sufficient to induce tumorigenesis when hormone levels were normalized by this method. This study demonstrates peroral administration can be used in long-term studies to elucidate relationships between different types and levels of steroid hormones.

show abstract

“…After this period, HT is thought to exert neutral or perhaps harmful neural effects (Henderson et al, 2005;Whitmer et al, 2011;Shao et al, 2012). Experimental animal studies parallel aspects of the human literature in that E2 treatment yields significant neural benefits in middle-aged females across several rodent paradigms (Pike et al, 2009), outcomes that are often attenuated in aged animals (Aenlle and Foster, 2010;Liu et al, 2015). Note, however, that E2 can exert positive neural effects, including improved behavioral performance, even in aged female mice (Frick et al, 2002;Vaucher et al, 2002).…”

Section: Discussionmentioning

confidence: 95%

Aging Reduces Estradiol Protection Against Neural but Not Metabolic Effects of Obesity in Female 3xTg-AD Mice

Christensen

Liu

Pike

2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

Vulnerability to Alzheimer's disease (AD) is increased by several risk factors, including midlife obesity, female sex, and the depletion of estrogens in women as a consequence of menopause. Conversely, estrogen-based hormone therapies have been linked with protection from age-related increases in adiposity and dementia risk, although treatment efficacy appears to be affected by the age of initiation. Potential interactions between obesity, AD, aging, and estrogen treatment are likely to have significant impact on optimizing the use of hormone therapies in postmenopausal women. In the current study, we compared how treatment with the primary estrogen, 17β-estradiol (E2), affects levels of AD-like neuropathology, behavioral impairment, and other neural and systemic effects of preexisting diet-induced obesity in female 3xTg-AD mice. Importantly, experiments were conducted at chronological ages associated with both the early and late stages of reproductive senescence. We observed that E2 treatment was generally associated with significantly improved metabolic outcomes, including reductions in body weight, adiposity, and leptin, across both age groups. Conversely, neural benefits of E2 in obese mice, including decreased β-amyloid burden, improved behavioral performance, and reduced microglial activation, were observed only in the early aging group. These results are consistent with the perspective that neural benefits of estrogen-based therapies require initiation of treatment during early rather than later phases of reproductive aging. Further, the discordance between E2 protection against systemic versus neural effects of obesity across age groups suggests that pathways other than general metabolic function, perhaps including reduced microglial activation, contribute to the mechanism(s) of the observed E2 actions. These findings reinforce the potential systemic and neural benefits of estrogen therapies against obesity, while also highlighting the critical role of aging as a mediator of estrogens' protective actions.

show abstract

Cognitive effects of long-term dydrogesterone treatment used alone or with estrogen on rat menopausal models of different ages

Cited by 15 publications

References 63 publications

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1

Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary Tumorigenesis in Ovariectomized Rats without Progesterone

Aging Reduces Estradiol Protection Against Neural but Not Metabolic Effects of Obesity in Female 3xTg-AD Mice

Contact Info

Product

Resources

About