Brain-derived estrogen and neural function

Brann, Darrell W.; Lu, Yujiao; Wang, Jing; Zhang, Quanguang; Thakkar, Roshni; Sareddy, Gangadhara R.; Pratap, Uday P.; Tekmal, Rajeshwar Rao; Vadlamudi, Ratna K.

doi:10.1016/j.neubiorev.2021.11.014

Cited by 79 publications

(62 citation statements)

References 308 publications

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“…Our results were in line with the estrogen levels associated with cycle length reported by Mumford et al [25], and were also consistent with those in previous studies that reported an association between memory and processes of encoding and recalling [60][61][62]. They are also in line with the estrogen synthesis of the brain, which takes place mostly in the hippocampus and temporal regions [63,64].…”

Section: Discussionsupporting

confidence: 93%

Influence of Menstrual Cycle Length and Age at Menarche on Symptoms, Cognition, Social Cognition, and Metacognition in Patients with First-Episode Psychosis

Barrau-Sastre

Birulés

Verdaguer-Rodríguez

et al. 2022

Women

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A protective effect has traditionally been attributed to estrogen in psychotic disorders. The aim of this study was to investigate cumulative lifetime estrogen by assessing the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and the age of menarche, measuring their effects on symptoms, cognition, social cognition, and metacognition. As it was not possible to directly measure cumulative estrogen levels over the lifetime of a patient, the study sample was composed of 42 women with first-episode psychosis; estrogen levels were inferred by the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and menarche. All patients were assessed with a battery of questionnaires using the BDI, PSYRATS, PANSS, STROOP, TAVEC, WSCT, IPSAQ, and BCIS questionnaires. The results related to menstrual cycle length showed a relationship with memory; specifically, shorter cycles with semantic strategies (p = 0.046) and longer cycles with serial strategies in the short term (p = 0.005) as well as in the long term (p = 0.031). The results also showed a relationship with perseverative errors (p = 0.035) and self-certainty (p = 0.049). Only personalized bias (p = 0.030) was found to be significant in relation to the age at menarche. When analyzing the differences in years of difference between the age at menarche and the onset of psychotic symptoms, the results indicated lower scores in women with a smaller difference between both events in memory (short-term (p = 0.050), long-term (p = 0.024), intrusions (p = 0.013), and recognition (p = 0.043)) and non-perseverative errors (p = 0.024). No relationship was found between symptoms and menstrual characteristics. The investigatory outcomes seem to indicate a relationship between estrogen cumulative effects and the memory domain. More in-depth investigations in the field are necessary in order to improve personalized treatment in women with psychosis.

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Section: Discussionsupporting

confidence: 93%

Influence of Menstrual Cycle Length and Age at Menarche on Symptoms, Cognition, Social Cognition, and Metacognition in Patients with First-Episode Psychosis

Barrau-Sastre

Birulés

Verdaguer-Rodríguez

et al. 2022

Women

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“…In contrast, hypothalamic estradiol concentrations in estradiol-replete female marmosets, estimated at ~48% of those in circulation, strongly suggest considerable additional factors limiting hypothalamic estradiol content, including elevated estradiol levels stimulating elevations in circulating SHBG concentrations, thus diminishing the amount of unbound estradiol, as well as estradiol inhibition of cytochrome b 5 expression in the hypothalamus, and likely 17,20 lyase activity, of estradiol-replaced female marmosets leading to diminished hypothalamic androgens and estrogens. Selective protection of the brain from circulating concentrations of steroid hormones, likely protects local brain production of estradiol in order to enable its action as a neurosteroid independent of ovarian function [ 13 , 148 , 149 ].…”

Section: Discussionmentioning

confidence: 99%

Aromatase Inhibition Eliminates Sexual Receptivity Without Enhancing Weight Gain in Ovariectomized Marmoset Monkeys

Kraynak

Willging

Kuehlmann

et al. 2022

Journal of the Endocrine Society

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Ovarian estradiol supports female sexual behavior and metabolic function. While ovariectomy (OVX) in rodents abolishes sexual behavior and enables obesity, OVX in nonhuman primates decreases, but does not abolish, sexual behavior, and inconsistently alters weight gain. We hypothesize that extra-ovarian estradiol provides key support for both functions, and to test this idea, we employed aromatase inhibition to eliminate extra-ovarian estradiol biosynthesis and diet-induced obesity to enhance weight gain. Thirteen adult female marmosets were OVX and received: (1) estradiol-containing capsules and daily oral treatments of vehicle (E2; n=5); empty capsules and daily oral treatments of either (2) vehicle (VEH, 1ml/kg, n=4), or (3) letrozole (LET, 1 mg/kg, n=4). After 7 months, we observed robust sexual receptivity in estradiol, intermediate frequencies in VEH, and virtually none in LET females (p=0.04). By contrast, few rejections of male mounts were observed in estradiol, intermediate frequencies in VEH, and high frequencies in LET females (p=0.04). Receptive head turns were consistently observed in estradiol, but not in VEH and LET females. LET females, alone, exhibited robust aggressive rejection of males. VEH and LET females demonstrated increased % body weight gain (p=0.01). Relative estradiol levels in peripheral serum were E2>>>VEH>LET, while those in hypothalamus ranked E2=VEH>LET, confirming inhibition of local hypothalamic estradiol synthesis by letrozole. Our findings provide the first evidence for extra-ovarian estradiol contributing to female sexual behavior in a nonhuman primate, and prompt speculation that extra-ovarian estradiol, and in particular neuroestrogens, may similarly regulate sexual motivation in other primates, including humans.

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“…In fact, postmenopausal women are most frequently affected by sporadic AD in a ratio 3:1, differently from the incidence in the infrequent hereditary illness occurring in younger patients in a ratio 1:1 ( 29 ). Estrogen deficiency occurring in spontaneous or surgical menopause has been associated to cognitive decline; in this context, several studies have shown that early E 2 replacement exerts neuroprotective effects ( 7 , 30 ).…”

Section: Menopause and Development Of Admentioning

confidence: 99%

“…Estradiol (E 2 ), the main estrogen acting during women´s reproductive years, is well known to exert neuroprotection through various mechanisms ( 3 – 5 ). Even more, neuron derived E 2 regulates synaptic plasticity and memory ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Menopause and development of Alzheimer’s disease: Roles of neural glucose metabolism and Wnt signaling

Villaseca

Cisternas²,

Inestrosa³

2022

Front. Endocrinol.

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Late onset Alzheimer´s disease (AD) is a neurodegenerative disease with gender differences in its onset and progression, being the prevalence predominant in women and at an earlier age than in men. The pathophysiology of the menopausal condition has been associated to this dementia, playing major roles regarding both endocrine and glucose metabolism changes, amongst other mechanisms. In the current review we address the role of estrogen deficiency in the processes involved in the development of AD, including amyloid precursor protein (APP) processing to form senile plaques, Tau phosphorylation forming neurofibrillary tangles, Wnt signaling and AD neuropathology, the role of glucose brain metabolism, Wnt signaling and glucose transport in the brain, and our research contribution to these topics.

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Brain-derived estrogen and neural function

Cited by 79 publications

References 308 publications

Influence of Menstrual Cycle Length and Age at Menarche on Symptoms, Cognition, Social Cognition, and Metacognition in Patients with First-Episode Psychosis

Influence of Menstrual Cycle Length and Age at Menarche on Symptoms, Cognition, Social Cognition, and Metacognition in Patients with First-Episode Psychosis

Aromatase Inhibition Eliminates Sexual Receptivity Without Enhancing Weight Gain in Ovariectomized Marmoset Monkeys

Menopause and development of Alzheimer’s disease: Roles of neural glucose metabolism and Wnt signaling

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