Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation

McEwen, Bruce S.; Akama, Keith T.; Alves, Stephen E.; Brake, Wayne G.; Bulloch, Karen; Lee, Susan; Li, Chenjian; Yuen, Genevieve S.; Milner, Teresa A.

doi:10.1073/pnas.121146898

Cited by 282 publications

(222 citation statements)

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“…Estrogen has been shown to modulate the functional state of the cholinergic system by increasing choline acetyltransferase (ChAT) activity and by increasing the release of Ach Pongrac et al, 2004). Researchers have also demonstrated that estrogen enhances NMDAR function by increasing NMDAR binding, at least in some brain regions, possibly by increasing the density of dendritic spines that express NMDAR (McEwen et al, 2001;Smith et al, 2009;Woolley and McEwen, 1994). Moreover, Daniel and Dohanich (2001) demonstrated that the influence of estrogen on NMDA receptor function is mediated specifically via M2 receptors.…”

Section: Discussionmentioning

confidence: 99%

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Furey

Khanna

Hoffman

et al. 2010

Neuropsychopharmacol

101

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Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 mg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group Â block interaction (F ¼ 21.0, po0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F ¼ 8.4, p ¼ 0.006). The treatment group Â block interaction was also significant in males (F ¼ 3.8, p ¼ 0.043) and females (F ¼ 35.6, po0.001) separately. A block Â gender interaction (F ¼ 7.4, p ¼ 0.009) indicated that the response magnitude was larger in women. The treatment Â block interaction was significant for the HAM-A across gender (F ¼ 12.0, po0.001), and was significant for females (F ¼ 24.9, po0.001) but not for males (F ¼ 1.3, p ¼ 0.30). When comparing the baseline block to study end, the block Â gender interaction (F ¼ 12.6, p ¼ 0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.

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Section: Discussionmentioning

confidence: 99%

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Furey

Khanna

Hoffman

et al. 2010

Neuropsychopharmacol

101

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“…It has been suggested that spinophilin may regulate local protein synthesis at the dendrites (28,54). In several recent studies, effects of E on local protein synthesis have been suggested (55), and IR for E receptor ␣ has been found in dendrites of hippocampal pyramidal neurons (56). Thus, the enhancement of spinophilin expression by E treatment may contribute to the maturation of spines in several ways.…”

Section: Discussionmentioning

confidence: 99%

Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice

Brake

Romeo

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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317

242

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Estrogen (E) treatment induces axospinous synapses in rat hippocampus in vivo and in cultured hippocampal neurons in vitro. To better explore the molecular mechanisms underlying this phenomenon, we have established a mouse model for E action in the hippocampus by using Golgi impregnation to examine hippocampal dendritic spine morphology, radioimmunocytochemistry (RICC) and silver-enhanced immunocytochemistry to examine expression levels of synaptic protein markers, and hippocampal-dependent object-placement memory as a behavioral readout for the actions of E. In ovariectomized mice of several strains and F 1 hybrids, the total dendritic spine density on neurons in the CA1 region was not enhanced by E treatment, a finding that differs from that in the female rat. E treatment of ovariectomized C57BL͞6J mice, however, caused an increase in the number of spines with mushroom shapes. By RICC and silver-enhanced immunocytochemistry, we found that the immunoreactivity of postsynaptic markers (PSD95 and spinophilin) and a presynaptic marker (syntaxin) were enhanced by E treatment throughout all fields of the dorsal hippocampus. In the object-placement tests, E treatment enhanced performance of object placement, a spatial episodic memory task. Taken together, the morphology and RICC results suggest a previously uncharacterized role of E in synaptic structural plasticity that may be interpreted as a facilitation of the spine-maturation process and may be associated with enhancement of hippocampal-dependent memory.D endritic spines are specialized to receive synaptic inputs and to compartmentalize calcium, and changes in spine morphology and function are considered to be important for processes such as learning and memory (1-5). It is, therefore, important to understand how dendritic spine formation and maturation are regulated. Extrinsic factors, such as circulating hormones, influence spine properties in the hippocampus. Estrogen (E) treatment regulates dendritic spine formation in the rat hippocampus in vivo (6-8) and in cultured hippocampal neurons in vitro (9-12). The effects of E on hippocampaldependent cognitive functions were shown also in rats and humans (13-15) and recently in mice and nonhuman primates (16)(17)(18)(19).Dendritic-spine changes include at least two different processes: generation of new spines and maturation of existing spine synapses. These processes are closely linked, with complex biochemical, morphological, and electrophysiological consequences (1,2,20). Spine maturation is a multistep, multifaceted process in which the spines change from thin filopodia-like structures to spines with bigger heads, larger synaptic contact area, shorter and wider spine necks, and newly recruited synaptic proteins (1,3,(20)(21)(22). In cell culture, only the mature type of dendritic spines can recruit ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (2) and, thus, make the transition from silent to functional synapses (23).Studies of E-induced synapse formation in the rat hippocampus have use...

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“…I submit that such a possibility should arouse the interest of neurotoxicologists; it is a research area that we should not abandon to endocrinologists. McEwen et al (2001) have a blunt message for us: "The brain is widely responsive to gonadal hormones. "…”

Section: Epiloguementioning

confidence: 99%

Can endocrine disruptors influence neuroplasticity in the aging brain?

Weiss

2007

NeuroToxicology

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Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer's disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, antiandrogens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle.

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Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation

Cited by 282 publications

References 123 publications

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice

Can endocrine disruptors influence neuroplasticity in the aging brain?

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