Multiple Pathways Transmit Neuroprotective Effects of Gonadal Steroids

Bryant, Damani N.; Sheldahl, Laird C; Marriott, Lisa K.; Shapiro, Robert A.; Dorsa, Daniel M.

doi:10.1385/endo:29:2:199

Cited by 91 publications

(54 citation statements)

References 194 publications

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“…It has been known for a number of years that estrogen has acute, membrane-initiated signaling actions in the brain (for review see (Kelly and Rønnekleiv, 2002, Bryant et al, 2006). The nature and significance of these actions have been a matter of dispute.…”

Section: Membrane-initiated Signaling Of E2mentioning

confidence: 99%

“…It has become clear that there are "indirect" genomic actions of estrogen in the brain that do not require nuclear targeting of estrogen receptors and therefore are classified as "membraneinitiated" signaling of estrogen (for review (Kelly and Levin, 2001, Bryant et al, 2006, Hammes and Levin, 2007). Such signals that are initiated by E2 at the plasma membrane can trigger intracellular signaling events that result in gene transcription.…”

Section: Membrane-initiated Signaling Of E2mentioning

confidence: 99%

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Membrane-initiated estrogen signaling in hypothalamic neurons

Kelly

Rønnekleiv

2008

Molecular and Cellular Endocrinology

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SummaryIt is well known that many of the actions of 17β-estradiol (E2) in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there is compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. But it is not well understood how estrogen signals via membrane receptors, and how these signals impact not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for sometime that E2 can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, E2 can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review will consider our current knowledge of rapid membrane-initiated and intracellular signaling by E2 in the hypothalamus, the nature of receptors involved and how they contribute to homeostatic functions. KeywordsERα; ERβ; GPCR (G protein-coupled receptor); mER (membrane estrogen receptor that is a GPCR) Electrophysiological studies in the 1960's and 1970's suggested that gonadal steroids could directly modulate the electrical activity of hypothalamic neurons

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Section: Membrane-initiated Signaling Of E2mentioning

confidence: 99%

Section: Membrane-initiated Signaling Of E2mentioning

confidence: 99%

Membrane-initiated estrogen signaling in hypothalamic neurons

Kelly

Rønnekleiv

2008

Molecular and Cellular Endocrinology

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“…Simultaneously, a large body of work on animal models emerged that provided compelling evidence for the potential of estrogen to alter synaptic circuitry in hypothalamus, hippocampus, and more recently neocortex (see section by J.H.M. ), as well as its capacity to be neuroprotective (Bryant et al, 2006). In addition, animal studies have demonstrated positive effects of ET on cognitive behavior, particularly in nonhuman primates (NHPs), although the extent and nature of cognitive enhancement varies with age (Lacreuse, 2006).…”

mentioning

confidence: 99%

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Morrison¹,

Brinton²,

Schmidt³

et al. 2006

J. Neurosci.

299

242

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IntroductionAs neuroscientists, we can be so taken by the complexity and unique capabilities of the brain that we occasionally forget that it is part of a larger integrated biological system reliant on signaling and communication throughout the organism. The interactions between key organs that release hormones (e.g., gonads) and the nervous system are an excellent reflection of this "whole-brain, whole-body" level of integration. For example, effects of estrogens such as 17-␤-estradiol (the major estrogen in most mammals, including women, referred to henceforward as estradiol) on a broad array of brain regions and the widespread distribution of estrogen receptors throughout the entire brain highlight the extraordinary integrative power of this hormone. An important concept in this interaction is that the brain both controls estrogen release through the hypothalamus-pituitary-gonadal (HPG) axis and responds to estrogen. Neuroendocrine function initiates in the hypothalamus (see below, section by A.C.G.) (Fig. 1), but the circuits that respond to estrogens go well beyond the hypothalamus to include neocortex, hippocampus, and brainstem. In addition, estradiol plays a key role in the neurobiology of aging, because endocrine and neural senescence overlap in time and are mechanistically intertwined in complex feedback loops. This aspect of aging is fundamental for humans, because all women will experience a dramatic drop in circulating estrogens if they live long enough to reach the menopause transition. Interestingly, at the turn of the past century, both life expectancy and the average age of onset of menopause for women in America was slightly over 50 years, whereas currently women can expect to live until 80 years of age, although the average age of menopause remains in

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“…Therefore, these results confirm the role of ER in memory, but cross-talk between ER and ER receptors cannot be excluded. It was also evidenced that rapid improvements in cognition could be mediated by membrane associated estrogen receptors activating mitogen-activated protein kinase (MAPK) signalling pathways in specific neural sites (Bryant et al, 2006). For example, estrogen enhances performance in tasks such as inhibitory avoidance (IA), object recognition and placement within 4h of treatment; a post-training paradigm evidenced that these effects are due to the facilitatory action of estrogen on memory (Frye et Walf & Frye, 2006).…”

Section: Estrogen In Learning and Memorymentioning

confidence: 99%