Acute responses to estradiol replacement in the olfactory system of apoE-deficient and wild-type mice

Nathan, Britto P.; Tonsor, Michael; Struble, Robert G.

doi:10.1016/j.brainres.2010.04.070

Cited by 10 publications

(7 citation statements)

References 49 publications

(55 reference statements)

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“…Interestingly, oestradiol has been shown to increase olfactory epithelial cell density and to have a protective role against olfactory function decline [30]. Additionally, in animal models of neurogenerative diseases oestradiol replacement prevents olfactory dysfunction [31]. This study was not powered to estimate the effect of menopause-driven differences in this subgroup.…”

Section: Discussionmentioning

confidence: 99%

Distorted chemosensory perception and female sex associate with persistent smell and/or taste loss in people with SARS-CoV-2 antibodies: a community based cohort study investigating clinical course and resolution of acute smell and/or taste loss in people with and without SARS-CoV-2 antibodies in London, UK

et al. 2021

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Background Loss of smell and/or taste are cardinal symptoms of COVID-19. ‘Long-COVID’, persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4–6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants. Methods Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4–6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations. Results People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p < 0.001) compared to female participants, who were almost 2.5-times more likely to have ongoing smell loss after 4–6 weeks (OR 2.46, 95%CI 1.47–4.13, p = 0.001). Female participants with SARS-CoV-2 antibodies and unresolved smell loss and unresolved taste loss were significantly older (> 40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54–4.00, p < 0.001). Conclusion Although smell and/or taste loss are often transient manifestations of COVID-19, 42% of participants had ongoing loss of smell, 34% loss of taste and 36% loss of smell and taste at 4–6 weeks follow-up, which constitute symptoms of ‘long-COVID’. Females (particularly > 40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions. Trials registration ClinicalTrials.govNCT04377815 Date of registration: 23/04/2020.

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Section: Discussionmentioning

confidence: 99%

Distorted chemosensory perception and female sex associate with persistent smell and/or taste loss in people with SARS-CoV-2 antibodies: a community based cohort study investigating clinical course and resolution of acute smell and/or taste loss in people with and without SARS-CoV-2 antibodies in London, UK

et al. 2021

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“…Although the synaptic integrity of the OB is also compromised in the APOE deficient mice (69), it is not yet known whether its regenerative capacity is also decreased or delayed. Interestingly, estrogen treatment has been shown to stimulate the regeneration of OE and synaptogenesis of OB in an APOE -dependent manner (70). …”

Section: Olfactory System In Aging and Admentioning

confidence: 99%

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Albers

Gilmore

Kaye

et al. 2014

Alzheimer's & Dementia

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465

379

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Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer’s disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and Alzheimer’s Disease”. The scientific sessions of the workshop focused on age-related and neuropathological changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the CNS are affected by Alzheimer pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.

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“…APOE facilitates the neuroprotective effects of estrogens and androgens. Estradiol-mediated increases in APOE result in neurite outgrowth in cultured mouse cortical neurons ( Nathan et al, 2004 ), and in neuronal maturation and synaptogenesis in the murine olfactory bulb ( Nathan et al, 2010 ). APOE is also required for estrogen-mediated neuroprotection in a mouse model of global ischemia ( Horsburgh et al, 2002 ).…”

Section: Apoe : a Sex-dependent Genetic Determinant In Loadmentioning

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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Acute responses to estradiol replacement in the olfactory system of apoE-deficient and wild-type mice

Cited by 10 publications

References 49 publications

At the interface of sensory and motor dysfunctions and Alzheimer's disease

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

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