Novel Mechanisms of Estrogen Action in the Brain: New Players in an Old Story

Cd, Toran-Allerand; Singh, Meharvan; Sétáló, György

doi:10.1006/frne.1999.0177

Cited by 406 publications

(238 citation statements)

References 120 publications

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“…It is important to note that this began with studies that identified a complementary expression of estrogen, estrogen receptors, and different members of the neurotrophin family, including NGF (nerve growth factor) and BDNF. This pattern of expression strongly suggested functional interactions, and these were predicted from the initial expression studies [4].…”

Section: Estrogen and Bdnf In Hippocampus A Rationalementioning

confidence: 66%

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

265

202

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In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy.

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Section: Estrogen and Bdnf In Hippocampus A Rationalementioning

confidence: 66%

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

265

202

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“…It is conceivable that protection of some cochlear or central auditory tissue was provided by estrogen, but these effects were masked by ABR threshold elevation which was caused by diminution of hair cell integrity. Estrogen is known to affect neural systems in a variety of ways that can be neuroprotective/positive or (less commonly) neurotoxic/negative (e.g., Belisle et al, 1985;Bergman et al, 1989;Bittar et al, 2001;Easton et al, 2006;GarciaSegura et al, 2001;Papalexi et al, 2005;Picazo et al, 2003;Toran-Allerand et al, 1999;Usui, 2006), leaving open many possibilities to be addressed by future research. Various lines of evidence suggest that ovarian hormones may affect auditory function directly (Coleman et al, 1994;Hultcrantz et al, 2006).…”

Section: Sex Differences In Control (Non-exposed) Mice and The Effectmentioning

confidence: 99%

Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms

et al. 2006

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Gonadectomized and surgically intact adult C57BL/6J (B6) mice of both sexes were exposed for 12 hours nightly to a high-frequency augmented acoustic environment (AAE): repetitive bursts of a half-octave noise band centered at 20 kHz, 70 dB SPL. The effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (exhibited by B6 mice) were evaluated by obtaining auditory brainstem response thresholds at ages 3-, 6-, and 9-months; hair cell counts (cytocochleograms) were obtained at 9 months. A sex difference in the rate of genetic progressive hearing loss in B6 mice (observed by earlier studies) was confirmed, with females exhibiting a faster rate of threshold elevations and more severe loss of hair cells at age 9 months. Gonadectomy had no consistent effects on the rate or severity of hearing loss in nonexposed mice of either sex. An unexpected finding was that the high-frequency AAE treatment caused additional ABR threshold elevations and hair cell loss. In an earlier study, the same high-frequency AAE treatment on DBA/ 2J mice ameliorated hearing loss. The most severe AAE-induced losses occurred in surgically intact females, suggesting a potentiating effect of ovarian hormone(s).

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“…13 The recent findings on estrogen-dependent attenuation of microglia response provide a novel explanation for hormone action in the brain and for the understanding of the neurodegenerative process in neural pathologies, like MS, AD or ischemic brain damage, in which inflammation plays a relevant role, and eventually also in schizophrenia or depression, where suggestive evidence indicates their association with local inflammation.…”

mentioning

confidence: 99%