Oophorectomy, Menopause, Estrogen, and Cognitive Aging: The Timing Hypothesis

Rocca, Walter A.; Grossardt, Brandon R.; Shuster, Lynne T.

doi:10.1159/000289229

Cited by 96 publications

(77 citation statements)

References 39 publications

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“…So, loss of Purkinje cells may result in subsequent granule cell death [42]. The current findings provided a plausible mechanism underlying the clinical observation of increased risk of Alzheimer ʼ s disease in women who had undergone oophorectomy prior to menopause [43,44].…”

Section: Discussionmentioning

confidence: 78%

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Ahmed¹,

Abdelrahman²,

Shalaby³

2017

J Cytol Histol

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Alterations in hormone levels during menopause affect cognitive function and brain chemistry. Stem cell therapy in nervous system disorders is a growing field. The present research aimed to compare the effect of MSCs with that of estradiol benzoate or avosoya on the cerebellum of ovariectomized rats. Fifty eight adult female Wistar albino rats were classified into five groups. Control group (Group I) and four ovariectomized groups. Group II (ovariectomized rats received no treatment), Group III (injected subcutaneously with estradiol benzoate), Group IV (received avosoya orally) and Group V (treated with human umbilical cord blood derived mesenchymal stem cells [HUCBMSCs]). Cerebellar sections were stained with hematoxylin and eosin and cresyl fast violet. Immunoperoxidase reaction of glial fibrillary acidic protein (GFAP), estrogen receptor beta (Erβ) and Bax protein was also done. HUCBMSCs homing in rat cerebellum were detected by human albumin gene. Antioxidant enzyme levels were also measured in cerebellum homogenate. Decreased density of neurons in the three cortical layers with vacuolations and distorted Purkinje cells with pyknotic nuclei were observed in Group II. Group III cerebellar cortex showed normal architecture but some Purkinje cells had pyknotic nuclei. Group IV showed normal neuronal cells in the three cortical layers. Group V Purkinje cells were pyriform with vesicular nuclei, and basophilic cytoplasm. Small rounded cells with deeply stained nuclei appeared in the granular layer. In conclusion: estradiol benzoate and avosoya improve ovariectomy-induced cerebellar alteration, and MSCs show promising results in this field.

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Section: Discussionmentioning

confidence: 78%

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Ahmed¹,

Abdelrahman²,

Shalaby³

2017

J Cytol Histol

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“…This lack of benefit of ERT may be explained by the critical period hypothesis, which proposes that there is a critical period after reproductive senescence during which estrogen is capable of increasing hippocampal function to a sufficient degree to enhance memory processing. After this period, ERT might be ineffective and possibly even detrimental (6,7).…”

mentioning

confidence: 99%

Duration of estrogen deprivation, not chronological age, prevents estrogen's ability to enhance hippocampal synaptic physiology

Smith

Vedder

Nelson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Whether estrogen replacement is beneficial to cognitive health is controversial. Some studies have shown that estrogen replacement therapy (ERT) relieves memory impairment associated with menopause in women, whereas others suggest that estrogen not only is incapable of providing a benefit, but actually can be detrimental. One possible explanation for this discrepancy in study findings could be the varying time after menopause at which ERT is initiated. It has been proposed that a critical period exists during which ERT must be administered to enhance cognitive function. This idea has yet to be tested directly using functional synaptic studies, however. Here we investigated whether prolonged hormone deprivation caused by ovariectomy (OVX) in young adult rats prevents the ability of estrogen replacement to increase synaptic function in the hippocampus to a degree necessary for estrogen-induced improvement in learning and memory. Remarkably, estrogen replacement was found to increase long-term potentiation, the current mediated by NR2B-containing NMDA receptors, and the dendritic spine density at CA3-CA1 synapses up to 15 months post-OVX. However, by 19 months post-OVX, the same estrogen replacement was unable to induce these changes. Importantly, this loss of estrogen's effectiveness was seen to be a consequence of the duration of deprivation. In female rats aged with their ovaries intact and examined at the same chronological age as the 19-month post-OVX group, estrogen replacement significantly increased synaptic function and spine density. These data clearly demonstrate that a critical period exists during which ERT must be administered, and that once this period passes, the beneficial effects are lost.C ognitive function fluctuates across the menstrual cycle in women, with increased learning occurring when plasma estrogen levels are highest (1, 2). As such, loss of endogenous estrogen production after menopause, a consequence of normal aging, has been correlated with cognitive deficits (3). Treatment with estrogen replacement therapy (ERT) is not always successful in alleviating this hormone-related cognitive decline (4, 5). This lack of benefit of ERT may be explained by the critical period hypothesis, which proposes that there is a critical period after reproductive senescence during which estrogen is capable of increasing hippocampal function to a sufficient degree to enhance memory processing. After this period, ERT might be ineffective and possibly even detrimental (6, 7).Hippocampal learning is increased during proestrus in cycling rats, and this effect can be mimicked in young adult ovariectomized (OVX) rats treated with the ovarian estrogen 17β-estradiol (E2) (8-11). Similar to women, rats that experience long-term ovarian hormone deprivation no longer benefit from E2's effects on enhancing hippocampal learning (12-15). The role of ovarian hormone senescence in the effectiveness of E2 replacement in enhancing learning is difficult to distinguish from normal aging processes, given that aging alone is kn...

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“…On the other hand, in a similar study, women with no history of depression, had increased levels of FSH and LH and increased variability of estradiol that were significantly associated with depressive symptoms (Freeman et al, 2006). In fact, it was proposed that the unstable and irregular pattern of hormone production during perimenopausal transition, in susceptible women, may increase vulnerability to mood disorders (Sherwin & Henry, 2008;Rocca et al, 2010).…”

Section: Monoamines and Depressionmentioning

confidence: 96%

Participation of the Monoaminergic System in the Antidepressant-Like Actions of Estrogens: A Review in Preclinical Studies

López‐Rubalcava¹,

Vega‐Rivera²,

Páez-Martínez³

et al. 2012

Effects of Antidepressants

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Oophorectomy, Menopause, Estrogen, and Cognitive Aging: The Timing Hypothesis

Cited by 96 publications

References 39 publications

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

Duration of estrogen deprivation, not chronological age, prevents estrogen's ability to enhance hippocampal synaptic physiology

Participation of the Monoaminergic System in the Antidepressant-Like Actions of Estrogens: A Review in Preclinical Studies

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