Rodent Models of Ovarian Failure

Marques-Lopes, José; Kempen, Tracey A. Van; Milner, Teresa A.

doi:10.1016/b978-0-12-811353-0.00060-9

Cited by 4 publications

(11 citation statements)

References 166 publications

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“…This is an ideal model to study the effect of ovarian hormones deficit and influence of exogenous hormonal treatments on the brain. Experimental interventions may occur either at the time of OVX or commence once 17β-estradiol has reached a low to non-detectable level in the plasma, which typically occurs within 1–2 weeks (Marques-Lopes et al, 2018).…”

Section: Rodent Models Of Menopausementioning

confidence: 99%

“…In early 2000s, the Hoyer group developed the innovative model of AOF that successfully replicates the human peri- and post-menopause stages, including irregular estrous fluctuations at peri-AOF (Mayer et al, 2004, 2005; Williams, 2005; Van Kempen et al, 2011, 2014), and acyclicity at post-AOF stage with very low estrogen levels, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels raising accordingly (Mayer et al, 2002; Van Kempen et al, 2011; Brooks et al, 2016; Marques-Lopes et al, 2018). In this model, 15-day administration of low doses of the 4-VCD (130–160 mg/Kg in 0.5% dimethyl sulfoxide in sesame oil; i.p.)…”

Section: Rodent Models Of Menopausementioning

confidence: 99%

“…Work from the Milner group established that this model is suitable for longitudinal studies (Van Kempen et al, 2014), and does not have any direct effects on induction of inflammation markers in brain areas inside (e.g., hippocampus and hypothalamus) and outside (e.g., circumventricular organs) the blood–brain barrier (Van Kempen et al, 2014). Based on the assessment of ovarian follicle depletion and responses of plasticity markers in brain areas known to be estrogen responsive, timepoints for pre-AOF (~25 days after first injection), peri-AOF (>58 days post-injection), and post-AOF (>139 days post-injection) stages have been established corresponding to the human pre-, peri-, and post-menopause, respectively (Mayer et al, 2004; Lohff et al, 2006; Van Kempen et al, 2011, 2014; Marques-Lopes et al, 2018; Figure 2). Length of peri-AOF period and beginning of post-AOF can be manipulated by varying the duration of VCD treatment (Brooks et al, 2016).…”

Section: Rodent Models Of Menopausementioning

confidence: 99%

“…Several laboratories have implemented this model to study cognition, cardiovascular disease, insulin resistance, atherosclerosis, bone loss, anxiety (Van Kempen et al, 2014), and hypertension (see next paragraph). A fairly recent summary of VCD doses and organs evaluated in studies applying the AOF model can be found in Van Kempen et al (2011) and Marques-Lopes et al (2018). A single study using the AOF has been reported in Tg2576 mouse model of AD.…”

Section: Rodent Models Of Menopausementioning

confidence: 99%

“…Rodent models have been constructed to replicate different elements of human menopause. These include natural aging, ovariectomy (OVX) and hormone replacement, and genetic models (Marques-Lopes et al, 2018). Although the current rodent models of menopause have and will continue to inform our understanding of the role of both estrogen and HRT in menopause, they fail to adequately recapitulate the human menopause process.…”

Section: Introductionmentioning

confidence: 99%

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Accelerated Ovarian Failure as a Unique Model to Study Peri-Menopause Influence on Alzheimer’s Disease

Marongiu

2019

Front. Aging Neurosci.

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Despite decades of extensive research efforts, efficacious therapies for Alzheimer’s disease (AD) are lacking. The multi-factorial nature of AD neuropathology and symptomatology has taught us that a single therapeutic approach will most likely not fit all. Women constitute ~70% of the affected AD population, and pathology and rate of symptoms progression are 2–3 times higher in women than men. Epidemiological data suggest that menopausal estrogen loss may be causative of the more severe symptoms observed in AD women, however, results from clinical trials employing estrogen replacement therapy are inconsistent. AD pathological hallmarks—amyloid β (Aβ), neurofibrillary tangles (NFTs), and chronic gliosis—are laid down during a 20-year prodromal period before clinical symptoms appear, which coincides with the menopause transition (peri-menopause) in women (~45–54-years-old). Peri-menopause is marked by widely fluctuating estrogen levels resulting in periods of irregular hormone-receptor interactions. Recent studies showed that peri-menopausal women have increased indicators of AD phenotype (brain Aβ deposition and hypometabolism), and peri-menopausal women who used hormone replacement therapy (HRT) had a reduced AD risk. This suggests that neuroendocrine changes during peri-menopause may be a trigger that increases risk of AD in women. Studies on sex differences have been performed in several AD rodent models over the years. However, it has been challenging to study the menopause influence on AD due to lack of optimal models that mimic the human process. Recently, the rodent model of accelerated ovarian failure (AOF) was developed, which uniquely recapitulates human menopause, including a transitional peri-AOF period with irregular estrogen fluctuations and a post-AOF stage with low estrogen levels. This model has proven useful in hypertension and cognition studies with wild type animals. This review article will highlight the molecular mechanisms by which peri-menopause may influence the female brain vulnerability to AD and AD risk factors, such as hypertension and apolipoprotein E (APOE) genotype. Studies on these biological mechanisms together with the use of the AOF model have the potential to shed light on key molecular pathways underlying AD pathogenesis for the development of precision medicine approaches that take sex and hormonal status into account.

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Section: Rodent Models Of Menopausementioning

confidence: 99%

Section: Rodent Models Of Menopausementioning

confidence: 99%

Section: Rodent Models Of Menopausementioning

confidence: 99%

Section: Rodent Models Of Menopausementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Accelerated Ovarian Failure as a Unique Model to Study Peri-Menopause Influence on Alzheimer’s Disease

Marongiu

2019

Front. Aging Neurosci.

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Sex and age influence gonadal steroid hormone receptor distributions relative to estrogen receptor β‐containing neurons in the mouse hypothalamic paraventricular nucleus

Contoreggi

Mazid

Goldstein

et al. 2021

J of Comparative Neurology

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Within the hypothalamic paraventricular nucleus (PVN), estrogen receptor (ER) β and other gonadal hormone receptors play a role in central cardiovascular processes. However, the influence of sex and age on the cellular and subcellular relationships of ERβ with ERα, G‐protein ER (GPER1), as well as progestin and androgen receptors (PR and AR) in the PVN is uncertain. In young (2‐ to 3‐month‐old) females and males, ERβ‐enhanced green fluorescent protein (EGFP) containing neurons were approximately four times greater than ERα‐labeled and PR‐labeled nuclei in the PVN. In subdivisions of the PVN, young females, compared to males, had: (1) more ERβ‐EGFP neurons in neuroendocrine rostral regions; (2) fewer ERα‐labeled nuclei in neuroendocrine and autonomic projecting medial subregions; and (3) more ERα‐labeled nuclei in an autonomic projecting caudal region. In contrast, young males, compared to females, had approximately 20 times more AR‐labeled nuclei, which often colocalized with ERβ‐EGFP in neuroendocrine (approximately 70%) and autonomic (approximately 50%) projecting subregions. Ultrastructurally, in soma and dendrites, PVN ERβ‐EGFP colocalized primarily with extranuclear AR (approximately 85% soma) and GPER1 (approximately 70% soma). Aged (12‐ to 24‐month‐old) males had more ERβ‐EGFP neurons in a rostral neuroendocrine subregion compared to aged females and females with accelerated ovarian failure (AOF) and in a caudal autonomic subregion compared to post‐AOF females. Late‐aged (18‐ to 24‐month‐old) females compared to early‐aged (12‐ to 14‐month‐old) females and AOF females had fewer AR‐labeled nuclei in neuroendrocrine and autonomic projecting subregions. These findings indicate that gonadal steroids may directly and indirectly influence PVN neurons via nuclear and extranuclear gonadal hormone receptors in a sex‐specific manner.

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Plasma Membrane Affiliated AMPA GluA1 in Estrogen Receptor β-containing Paraventricular Hypothalamic Neurons Increases Following Hypertension in a Mouse Model of Post-menopause

et al. 2019

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Rodent Models of Ovarian Failure

Cited by 4 publications

References 166 publications

Accelerated Ovarian Failure as a Unique Model to Study Peri-Menopause Influence on Alzheimer’s Disease

Accelerated Ovarian Failure as a Unique Model to Study Peri-Menopause Influence on Alzheimer’s Disease

Sex and age influence gonadal steroid hormone receptor distributions relative to estrogen receptor β‐containing neurons in the mouse hypothalamic paraventricular nucleus

Plasma Membrane Affiliated AMPA GluA1 in Estrogen Receptor β-containing Paraventricular Hypothalamic Neurons Increases Following Hypertension in a Mouse Model of Post-menopause

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