Estrogen neuroprotection and the critical period hypothesis

Abstract

17β-estradiol (estradiol or E2) is implicated as a neurodegenerative disorders. This review focuses on the mechanisms underlying E2 neuroprotection in cerebral ischemia, as well as emerging evidence from basic science and clinical studies, which suggests that there is a “critical period” for estradiol's beneficial effect in the brain. Potential mechanisms underlying the critical period are discussed, as are the neurological consequences of long-term E2 deprivation (LTED) in animals and in humans after natural menopause or surgical menopause. We also summarize the major clinical trials concerning postmenopausal hormone therapy (HT), comparing their outcomes with respect to cardiovascular and neurological disease and discussing their relevance to the critical period hypothesis. Finally, potential caveats, controversies and future directions for the field are highlighted and discussed throughout the review.

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

“…There is a considerable amount of evidence indicating that the rapid actions of 17b-estradiol in the nervous system involve activation of multiple kinase pathways, including the mitogen-activated protein kinase (MAPK)/ ERK pathway, the phospholipase C (PLC) pathway, PKC, PI3K/Akt (also referred to as protein kinase B), and PKA pathways Scott et al, 2012). Despite the canonical concept of ERs as transcription factors, it is clear now that the ERa, ERb, and the G-protein-coupled receptor (GPCR), G protein-coupled estrogen receptor 1 (also known as GPR30) can mediate rapid estrogenic signaling (Brinton, 2009;Prossnitz and Barton, 2011;, providing a mechanism for coupling rapid estrogenic signaling with intracellular signaling cascades.…”

“…2). It is also possible that the different rapid effects of 17b-estradiol are mediated by different combinations of the above receptor types in different neuronal cell types (Raz et al, 2008;Spary et al, 2009;Scott et al, 2012;Akama et al, 2013;Srivastava and Evans, 2013). There is also increasing evidence that a subpopulation of ERs are found at extranuclear sites and specifically at synapses, a subcellular localization consistent with the ability of these receptors to couple to second messenger signaling pathways.…”

Hip Fracture After Stroke in the Elderly: Trends in the Beginning of the 21st Century and Projections into the Future in Australia

“…75 On the other hand, while debate on risks and benefits of menopausal hormone therapy for stroke prevention continued over the last decade, 76,77 emerging data emphasized the neuroprotective effect of oestrogens 78 and increased risk of cerebral ischaemia in animal models with long-term oestrogen deprivation and loss of α-oestrogen receptor. [79][80][81] This complex issue deserves further intensive research to determine timing of initiation, safety and efficacy of formulation, dose (e.g. low-dose transdermal hormone therapy, selective oestrogen receptors modifiers) and duration.…”

<p>The Rise of the Physical Sciences in &ldquo;Stricto Sensu&rdquo; The Developmental Approach and the History of Sciences</p><p><br></p>

“…As mentioned, adult Pirãha cannot learn anymore to draw a straight line or to enumerate 1, 2 and 3, while their children can learn it when exposed to some training. Correspondingly, adult primitives living in their premodern societies do not surmount childlike psychological stages, even not later in their lifetimes when being 50 or 70 years old, as the whole ethnological literature evidences (Everett, 2008;Scott et al, 1951;Allier, 1929;Werner, 1948;Oesterdiekhoff, 2016c;2013a).…”

“…The phenomenon of arrested development explains the far-reaching commonalities between (modern) children and premodern adults right across the whole range of world understanding and psychological phenomena (Allier, 1929;Flynn, 2007;Werner, 1948;Hallpike, 1979;Luria, 1982;Mogdil and Mogdil, 1976, vol. 8;Oesterdiekhoff, 2012b;2013a;2013b;2016a;2016b;2016c;Scott et al, 1951).…”