Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Dumas, Julie A.; Hancur-Bucci, Catherine; Naylor, Magdalena R.; Sites, Cynthia K.; Newhouse, Paul

doi:10.1016/j.yhbeh.2007.09.011

Cited by 92 publications

(101 citation statements)

References 64 publications

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“…Whether there are interactions with the cholinergic (and/or other neurotransmitter) systems that change with aging and can mitigate steroids' cognitive effects is of interest [5,19]. It is likely that some of the effects are due to actions of 3α,5α-THP.…”

Section: Rotarodmentioning

confidence: 99%

Progesterone enhances performance of aged mice in cortical or hippocampal tasks

Frye

Walf

2008

Neuroscience Letters

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Ovarian steroids alter cognitive performance of young individuals. Whether progesterone enhances learning and memory in tasks involving the prefrontal cortex and/or hippocampus in aged mice was investigated. Aged mice received progesterone (10 mg/kg, SC) or vehicle and were tested for cortical and/or hippocampal learning and memory. Progesterone increased spontaneous alterations in the Tmaze and time spent exploring novel objects in the object recognition task. Progesterone increased the time mice spent in the quadrant of the water maze where the hidden platform had been during training, increased latencies to crossover to the shock-associated side of the inhibitory avoidance chamber, and increased freezing in the contextual fear conditioning task. Progesterone did not enhance performance in tasks mediated by the amygdala (cued conditioning), striatum (conditioned place preference), or cerebellum (rotarod) in these aged mice. Thus, progesterone improved learning and memory in tasks mediated by the prefrontal cortex and/or hippocampus of aged mice. KeywordsCognition; Learning; Memory; Estrogen Variations in cognitive performance of female rodents over reproductive cycles coincide with changes in levels of hormones, such as 17β-estradiol (E 2 ) and progesterone (P 4 ). Rats in behavioral estrus, compared to diestrus, have higher levels of E 2 and P 4 and perform better in inhibitory avoidance, trace conditioning, object recognition and placement tasks [9,26,39,41], but not active avoidance or water maze tasks [6,8]. Pregnant rats' performance in the water maze task is enhanced when E 2 and P 4 levels are escalating (1st and 2nd trimester), not declining (3rd trimester), compared to non-pregnant rats [18]. Thus, changes in endogenous hormones influence cognitive performance. E 2 and P 4 administration can improve cognitive performance of rodents. E 2 improves cognitive performance of young and aged rodents across a variety of tasks, but these effects are clearly influenced by age and the dosing/regimen utilized [4]. P 4 to young, middle-aged, or aged E 2 -primed rats or mice improves cognitive performance in several tasks [10,12,20,22,27,28].P 4 , independent of E 2 , may improve cognitive behavior. Chronic low-dose P 4 , or acute administration of P 4 , prior to training in the water maze improves performance of young, ovariectomized (ovx) rats [12]. P 4 post-training to ovx rats enhances performance in the object recognition, delayed-non-matching-to-sample, and inhibitory avoidance tasks, when rats were tested 24 h later when P 4 levels are at nadir [10]. Thus, physiological levels of P 4 , independent of E 2 , may enhance learning and memory of young adult rodents.

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Section: Rotarodmentioning

confidence: 99%

Progesterone enhances performance of aged mice in cortical or hippocampal tasks

Frye

Walf

2008

Neuroscience Letters

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“…Estradiol reduced the effects of nicotinic and muscarinic acetylcholine antagonism on tests of attention and verbal learning and memory (Dumas et al, 2008;Dumas et al, 2006). TMX has estrogen-like effects on the central, cholinergic system, supporting the possibility of estrogen-like enhancements on cognition (McMillan et al, 2002).…”

Section: Introductionmentioning

confidence: 93%

“…Studies in our (Dumas et al, 2008;Dumas et al, 2006;Dumas et al, 2012) and other labs revealed that estrogen acts in part through the cholinergic system to benefit cognition (as reviewed by Gibbs (2010)). Estradiol reduced the effects of nicotinic and muscarinic acetylcholine antagonism on tests of attention and verbal learning and memory (Dumas et al, 2008;Dumas et al, 2006).…”

Section: Introductionmentioning

confidence: 94%

“…Using an established model (Dumas et al, 2008;Dumas et al, 2006;Dumas et al, 2012) to show the effects of estradiol on cholinergic-related cognitive functioning, the study presented here examined whether cognitive impairments caused by cholinergic antagonists in healthy postmenopausal women were affected by 3 months of prior TMX treatment. Participants completed evaluations of attention, verbal memory and spatial learning and memory under the influence of a placebo or a muscarinic (scopolamine; SCOP) and/or nicotinic (mecamylamine; MECA) acetylcholine antagonist.…”

Section: Introductionmentioning

confidence: 99%

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Tamoxifen Improves Cholinergically Modulated Cognitive Performance in Postmenopausal Women

Newhouse

Albert

Astur

et al. 2013

Neuropsychopharmacol

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Tamoxifen (TMX) is a selective estrogen receptor modulator that is used as an estrogen receptor antagonist for the treatment and prevention of breast cancer. Whether TMX has antagonist activities in the human brain is less clear and its effects on cognitive function have not been experimentally explored. This study examined how TMX affected cognitive performance in older women using a model of anticholinergic drug-induced cognitive dysfunction. Twenty-one postmenopausal women were administered 20 mg of oral TMX or placebo for 3 months. Participants then took part in five drug challenges using the anticholinergic antinicotinic agent mecamylamine (MECA) and antimuscarinic agent scopolamine (SCOP) and were tested on a comprehensive battery including tasks of attention and psychomotor function, verbal episodic memory, and spatial navigation. After a 3-month placebo washout, participants were then crossed over to the alternate treatment and repeated the drug challenges after 3 months. Compared with placebo treatment, TMX significantly attenuated the impairment from cholinergic blockade on tasks of verbal episodic memory and spatial navigation, but effects on attentional/psychomotor tasks were more variable. Analysis by APOE genotype showed that APO e4 þ women showed a greater beneficial effect of TMX on reversing the cholinergic impairment than APO e4 À women on most tasks. This study provides evidence that TMX may act as an estrogen-like agonist to enhance cholinergic system activity and hippocampally mediated learning.

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“…Neuroprotection in Perimenopausal Women http://dx.doi.org/10.5772/intechopen.74330 135 and macrophages to 17β-E2 [90], and this fact may be an explanation of some studies showing better results with ET on memory recall in women aged around 70 and 20 years postmenopausal, if women have not demonstrated memory impairment [91].…”

Section: Sex Hormones In Neurodegenerative Processes and Diseases 132mentioning

confidence: 99%

Neuroprotection in Perimenopausal Women

Russu¹,

Antonescu²

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Endocrine and neural senescence overlap in time, by intertwined complex feedback loops. Womens' brain is genetically more prone to suffer during life, and perimenopause is a "critical period" in neuroaging, when the degenerative processes begin. Many hypotheses on the multifactorial nature of women's brain aging are elaborated, and tested in high-tech research centers. The most analyzed Alzheimer's disease (AD) is characterized not only by Aβ oligomers and fibrils accumulation, but also by metabolic and inflammatory changes, with the onset during menopausal transition and early years of menopause. Deep analysis of endocrine, neural, and metabolic pathways are giving new insights to the sequential view of Aβ-centric in AD pathogenesis, prevention, and treatment from perimenopause, for maintaining women's neurological health.

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Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Cited by 92 publications

References 64 publications

Progesterone enhances performance of aged mice in cortical or hippocampal tasks

Progesterone enhances performance of aged mice in cortical or hippocampal tasks

Tamoxifen Improves Cholinergically Modulated Cognitive Performance in Postmenopausal Women

Neuroprotection in Perimenopausal Women

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