"Neural mechanisms for chronic and acute effects of estrogens Background Ample evidence exists that estrogens cause morphologic and neurochemical changes in many areas of the brain when given acutely or chronically to animals or humans. Chronic treatments alter the major neuronal systems of the brain including, but not limited to, cholinergic, monoaminergic, GABAergic and glutaminergic neurons in both animals and humans (Gibbs, 2010; McEwen and Alves, 1999 "
[Show abstract][Hide abstract] ABSTRACT: A historical perspective on estradiol’s enhancement of cognitive function is presented, and research, primarily in animals, but also in humans, is reviewed. Data regarding the mechanisms underlying the enhancements are discussed. Newer studies showing rapid effects of estradiol on consolidation of memory through membrane interactions and activation of inter-cellular signaling pathways are reviewed as well as studies focused on traditional genomic mechanisms. Recent demonstrations of intra-neuronal estradiol synthesis and possible actions as a neurosteroid to promote memory are discussed. This information is applied to the critical issue of the current lack of effective hormonal (or other) treatments for cognitive decline associated with menopause and aging. Finally, the critical period hypothesis for estradiol effects is discussed along with novel strategies for hormone/drug development. Overall, the historical record documents that estradiol positively impacts some aspects of cognitive function, but effective therapeutic interventions using this hormone have yet to be realized.
Hormones and Behavior 09/2014; 66(4). DOI:10.1016/j.yhbeh.2014.08.011 · 4.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estradiol (E) has been suggested to have a neuroprotective effect in young animals but has neutral or harmful effects when it is administered to aged animals. In the present study, we determined whether the post-ovariectomy (post-OVX) timeframe elapsed before the initiation of chronic E treatment is critical for the estrogenic induction of neurotrophins (brain-derived neurotrophic factor, BDNF, and synaptophysin, SYN) in the rodent hippocampus. Adult mice were OVX and, a short period (short-term E (STE) animals) or a long period (long-term E (LTE) animals) after the OVX, were daily treated with E. Control animals were treated with sesame oil (short-term control (STC) and long-term control (LTC) animals). Protein expression was determined using an immunohistochemical approach. Transcriptional activity in the hippocampus of individual BDNF promoters was assessed by real-time quantitative RT-PCR, and the methylation levels of regulatory regions were analyzed by methylation-specific PCR and combined bisulfite restriction analysis. STE animals showed increased BDNF and SYN protein expression and a higher activity of BDNF II, IV and V promoters. In contrast, LTE animals did not show E induction of neurotrophins. In these animals, the methylation levels of regulatory sequences of the BDNF were higher than in the STE animals in a CpG island of promoter V and in the CRE regulatory site located in promoter IV. With this experiment, we determined that a prolonged period of hypoestrogenicity disrupts the E-induction of neurotrophins, and we postulated that DNA methylation is one of the epigenetic mechanisms that could explain the E-insensitivity of the BDNF after a long period post-OVX.
The Journal of Steroid Biochemistry and Molecular Biology 08/2014; 144. DOI:10.1016/j.jsbmb.2014.08.001 · 4.05 Impact Factor
"These include ischaemia, trauma, infection and neurodegeneration, where estrogens can activate various non-specific processes involved in cell survival, such as mitochondrial function, anti-oxidant activity and effects on gene products involved in regulating apoptosis. These mechanisms, along with considerations of whether estradiol's protective effects involve the classical nuclear estrogen receptors (ER), ERa or ERb, or the more recently recognised G protein-coupled receptor, GPER1 (also termed GPR30), are covered in many extensive reviews (Bourque et al., 2012; McEwen and Alves, 1999; Brann et al., 2007; Wise et al., 2001; Garcia-Segura et al., 2001; Raz et al., 2008; Behl, 2002; Green and Simpkins, 2000). Therefore, here we shall comment only on the relatively sparse information which may be relevant to PD and sex differences. "
[Show abstract][Hide abstract] ABSTRACT: Parkinson’s disease (PD) displays a greater prevalence and earlier age at onset in men. This review addresses the concept that sex differences in PD are determined, largely, by biological sex differences in the NSDA system which, in turn, arise from hormonal, genetic and environmental influences. Current therapies for PD rely on dopamine replacement strategies to treat symptoms, and there is an urgent, unmet need for disease modifying agents. As a significant degree of neuroprotection against the early stages of clinical or experimental PD is seen, respectively, in human and rodent females compared with males, a better understanding of brain sex dimorphisms in the intact and injured NSDA system will shed light on mechanisms which have the potential to delay, or even halt, the progression of PD. Available evidence suggests that sex-specific, hormone-based therapeutic agents hold particular promise for developing treatments with optimal efficacy in men and women.
Frontiers in Neuroendocrinology 08/2014; 35(3). DOI:10.1016/j.yfrne.2014.02.002 · 7.58 Impact Factor
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