Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in middle-aged female mice

Guimarães, Rebecca A.M.; Asth, Laila; Engelberth, Rovena Clara Galvão Januário; Cavalcante, Jeferson de Souza; Soares-Rachetti, Vanessa de Paula; Gavioli, Elaine C.

doi:10.1016/j.physbeh.2015.05.009

Cited by 15 publications

(10 citation statements)

References 45 publications

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“…For example, spatial reference memory decline begins at an earlier age in females than in males, a finding that may be related to the cessation of estrous cycling (Frick et al, 2000). It has been shown that the spontaneous failure of the estrous cycle increased anxiety, suggesting that the perimenopausal period has a significant influence on anxiety-related behaviors in female (Guimarães et al, 2015). The use of factorial analyses would make it possible to identify the motivational drivers underlying the spontaneous behavior of both sexes at different periods in their lives and to identify possible relationships between the indices of the different tests.…”

Section: Discussionmentioning

confidence: 99%

Deficits in Social Behavior Precede Cognitive Decline in Middle-Aged Mice

Boyer

Jaouen

Ibrahim

et al. 2019

Front. Behav. Neurosci.

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An extensive literature details deterioration of multiple brain functions, especially memory and learning, during aging in humans and in rodents. In contrast, the decline of social functions is less well understood. It is presently not clear whether age-dependent deficits observed in social behavior mainly reflect the disruption of social networks activity or are simply secondary to a more general impairment of cognitive and executive functions in older individuals. To address this issue, we carried out a battery of behavioral tasks exploring different brain functions in young (3 months) and middle-aged wild-type mice (9 months). Consistent with previous reports, our results show no obvious differences between these two groups in most of the domains investigated including learning and memory. Surprisingly, in social tasks, middle-aged animals showed significantly reduced levels of interactions when exposed to a new juvenile mouse. In the absence of overt cognitive decline, our findings suggest that social impairments may precede the disruption of other brain functions and argue for a selective vulnerability of social circuits during aging.

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Section: Discussionmentioning

confidence: 99%

Deficits in Social Behavior Precede Cognitive Decline in Middle-Aged Mice

Boyer

Jaouen

Ibrahim

et al. 2019

Front. Behav. Neurosci.

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“…The reproductive cycles in humans or the estrous cycle in mice are both under the influence of the hpg axis [ 39 , 40 ]. The effects are most drastic during puberty.…”

Section: Discussionmentioning

confidence: 99%

Long-Term High Fat Diet Has a Profound Effect on Body Weight, Hormone Levels, and Estrous Cycle in Mice

Chakraborty

Donthireddy²,

Adhikary³

et al. 2016

Med Sci Monit

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BackgroundObesity causes several health complications along with disruption of the reproductive system. The aim of the current study was to determine how long-term intake of very high fat diet (VHFD) changes the hormonal milieu, affecting the cellular morphology and reproductive cycle in female mice.Material/MethodsMice were fed on normal diet (ND) and VHFD for 2 weeks, 12 weeks, and 25–27 weeks. We assessed changes in body weight, food consumption, energy intake, cellular and tissue morphology, hormonal levels (leptin, insulin, and estradiol), and vaginal smears were performed at various time points to determine the length and cellularity at each stage of the estrous cycle.ResultsMice fed on VHFD showed a significant increase in weight gain, reduction in food intake, and increase in energy intake compared to animals fed on ND, indicating that the caloric density of the diet is responsible for the differences in weight gain. Hormonal analysis showed hyperleptinemia, hyperinsulinemia, and increases in estrogen levels, along with increases in size of the islet of Langerhans and adipocytes. After 25–27 weeks, all animals fed on VHFD showed complete acyclicity; elongation of phases (e.g., diestrous), skipping of phases (e.g., metestrous), or a combination of both, indicating disruption in the reproductive cycle. Quantitative analysis showed that in the diestrous phase there was a 70% increase in cell count in VHFD compared to animals fed on ND.ConclusionsThe above results show that morphological and hormonal changes caused by VHFD probably act via negative feedback to the hypothalamic-pituitary axis to shut down reproduction, which has a direct effect on the estrous cycle, causing acyclicity in mice.

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“…Several transgenic animal models harboring LOAD-related genetic modifications exhibit more severe disease-like phenotypes in females than males ( Schmid et al, 2019 ; Wang et al, 2003 ; Yue et al, 2011 ). Although female rodents do not undergo menopause, they do experience a period of altered estrous cycling ( Guimarães et al, 2015 ) followed by persistently low estrogen levels at old ages ( Felicio et al, 1984 ), similar to peri- and post-menopause in women. Findings from these models are in agreement with two possibilities in humans: (1) reduced estrogen exposure in adult females exacerbates disease progression, as in J20 mice ( Box 1 ) ( Broestl et al, 2018 ); and/or (2) the organizational effects of sex hormones during neurodevelopment have lasting effects that increase susceptibility to neurodegenerative disease later in life, as in 3xTgAD mice ( Box 1 ) ( Carroll et al, 2010 ).…”

Section: Findings From Animal Modelsmentioning

confidence: 99%

Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders

Gamache

Yun

Chiba‐Falek

2020

Disease Models &Amp; Mechanisms

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The importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk and endophenotypes have yet to be explained. In this Review, we revisit the different aspects of APOE involvement in neurodegeneration and neurological diseases, with particular attention to sex differences in the contribution of APOE to LOAD susceptibility. We discuss the role of APOE in a broader range of age-related neurodegenerative diseases, and summarize the biological factors linking APOE to sex hormones, drawing on supportive findings from rodent models to identify major mechanistic themes underlying the exacerbation of LOAD-associated neurodegeneration and pathology in the female brain. Additionally, we list sex-by-genotype interactions identified across neurodegenerative diseases, proposing APOE variants as a shared etiology for sex differences in the manifestation of these diseases. Finally, we present recent advancements in ‘omics’ technologies, which provide a new platform for more in-depth investigations of how dysregulation of this gene affects the development and progression of neurodegenerative diseases. Collectively, the evidence summarized in this Review highlights the interplay between APOE and sex as a key factor in the etiology of LOAD and other age-related neurodegenerative diseases. We emphasize the importance of careful examination of sex as a contributing factor in studying the underpinning genetics of neurodegenerative diseases in general, but particularly for LOAD.

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Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in middle-aged female mice

Cited by 15 publications

References 45 publications

Deficits in Social Behavior Precede Cognitive Decline in Middle-Aged Mice

Deficits in Social Behavior Precede Cognitive Decline in Middle-Aged Mice

Long-Term High Fat Diet Has a Profound Effect on Body Weight, Hormone Levels, and Estrous Cycle in Mice

Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders

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