Luis M Garcia-Segura

..Conversely, IGF-I regulates ERalpha transcriptional activity in neuroblastoma cells and the PI3K/Akt/GSK3 signaling pathway is involved in this effect...

..Therefore, it is important to determine whether aging affects the signaling of estradiol and IGF-I in the brain...

..The glial cells, therefore, are central to the coordination of endocrine and local inputs that bring about neural plasticity and adapt reproductive capacity to homeostatic signals...

..This special issue of Frontiers in Neuroendocrinology contains a collection of reviews of the most recent ideas and findings on these various aspects of sex steroid-dependent neuroprotection..

..Current investigations are evidencing the role exerted by key signalling molecules, such as glycogen synthase kinase 3 and beta-catenin, in the cross-talk of estrogen receptors and IGF-I receptors in neural cells...

..Aromatase may thus represent an important pharmacological target for therapies conducted to prevent aging-associated neurodegenerative disorders...

..abstract:..

....

..These findings indicate that estradiol, raloxifene, and tamoxifen are potential candidates for the control of astrogliosis in young and older individuals and after a prolonged depletion of ovarian hormones...

..This raises the possibility that the up-regulation of StAR expression and the subsequent modifications in steroidogenesis may be part of the mechanisms used by the brain to cope with neurodegeneration...

....

....

..Genistein showed neuroprotective effects only at high dose (10 mg/kg), suggesting that other components in the soy extract are involved in the neuroprotective effect...

..Here we report that tamoxifen and raloxifene decrease immobility time in the forced swim test and increases the time spent in open arms in the elevated plus maze in ovariectomized mice submitted to chronic unpredictable stress...

..The regulation of gliosis may be part of the neuroprotective mechanism of testosterone...

..Therefore, glial cells are important players in the neuroprotective and reparative mechanisms of estrogenic compounds...

..In addition, glial cells are targets for steroids and mediate some of the effects of these molecules on neurons, including the regulation of survival and regeneration...

....

..New SERMs with specific actions on neurons and glial cells may represent promising therapeutic tools for the brain...

..The findings support the potential therapeutic role of oestrogenic compounds as protective anti-inflammatory agents for the central nervous system...

..The widespread expression of aromatase in a large population of neurons in the normal and damaged hippocampus suggests that local estrogen formation may play an important role in human hippocampal function...

....

..Thus, our findings indicate that age affects the outcome of estradiol therapy in the brain...

..These findings suggest that the PBR is involved in control of neuronal survival and gliosis after brain injury and identify this molecule as a potential target for neuroprotective interventions...

....

....

..By analogy to the implication of aromatase into the growth of other forms of estrogen-sensitive tumors, such as some breast cancers, it is conceivable that the expression of aromatase may play a role in the growth of glioblastomas...

....

..These findings indicate that extragonadal estradiol exerts a neuroprotective effect in both sexes, which prevents neuronal loss as a consequence of mild neurodegenerative signals...

..In this study we have explored whether prenatal stress results in alterations in the immune response in the hippocampus of female mice during adult life...

....

..Therefore, steroidogenic acute regulatory protein, peripheral-type benzodiazepine receptor and aromatase are attractive pharmacological targets to promote neuroprotection in the aged brain...

..In turn, IGF-I may regulate ER transcriptional activity in neuronal cells. In conclusion, ERs appear to be part of the signaling mechanism of IGF-I, and IGF-I receptor part of the mechanism of estradiol signaling in the nervous system...

..The regulation of Tau expression and phosphorylation by progesterone may contribute to the hormonal regulation of cerebellar function by the modification of neuronal cytoskeleton...

..These findings suggest that estradiol formation by aromatase mediates neuroprotective effects of pregnenolone and DHEA against excitotoxic-induced neuronal death in the hippocampus...

..These findings suggest that estrogen effects in the brain may be mediated in part by the activation of the signaling pathways of the IGF-I receptor...

..This article is part of a Special Issue entitled 'Neurosteroids'...

..These changes could condition the response of this axis to future physiological and pathophysiological situations...

..Finally, this in vitro neuroinflammation model was fully inhibited, as demonstrated by ELISA and qPCR, by five selective oestrogen receptor modulators...

....

..However, the precise functional consequences of the regulation of reactive gliosis by gonadal hormones under acute and chronic neurodegenerative conditions are still not fully clarified...

..In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex...

..These results suggest that neuroactive steroids such as progesterone and dihydroprogesterone may represent therapeutic alternatives to counteract peripheral myelin alterations induced by diabetes...

..Therefore, glial cells are a key element to understanding hormonal actions in the nervous system and the regulation of neuroendocrine events...

..This finding suggests that estradiol may regulate arginine vasopressin levels on the supraoptic and paraventricular nuclei by acting on afferent neurons expressing estrogen receptor alpha...

..Therefore, a prolonged deprivation of ovarian hormones may represent a risk factor for the development of depressive and anxiety symptoms after the exposure to stressful experiences...

..These findings suggest that GPER participates in the control of hippocampal neuritogenesis by a mechanism involving the activation of PI3K signaling...

..These findings indicate that prenatal stress induces a basal proinflammatory status in the hippocampal formation during adulthood that results in an enhanced activation of microglia and astrocytes in response to a proinflammatory insult...

..3 aromatase transcripts. The cell specific regulation of CYP19A1 by vitamin D, dexamethasone, and mifepristone opens the possibility for cellular selective modulation of estrogen biosynthesis within the brain...

..These effects are likely to be mediated at least in part by the conversion of DHEA to estradiol...

..We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis...

..These findings suggest that estrogen effects in the hypothalamus may be mediated in part by the activation of the signaling pathways of the IGF-I receptor...

..This enhanced understanding of the mechanics of gonadotrophin control clarifies elements of the involved feedback loops and opens the way to a better understanding of the neurobiology of reproduction...

..These findings support the potential role of PBR ligands to prevent aging-associated peripheral nerve degeneration...

..The effects of DHEA on the hypothalamic IGF-1 system may be highly relevant to the control and maintenance of hypothalamic neuroendocrine function...

..ERKOalpha mice are more susceptible to MPTP toxicity and not protected by estradiol; differences in ERKObeta mice are subtler. These results suggest therapeutic potential for the brain of ER specific agonists...

..In addition, Akt and glycogen synthase kinase 3beta are key molecular targets to explain the interaction of oestrogen and IGF-I receptor signalling in the promotion of neuroprotection...

..In summary, our findings suggest that ER-dependent gene expression in N2a cells is controlled by the PI3K/Akt/GSK3 signaling pathway...

..Delta5-Diol increased GSK3beta phosphorylation less than the PPT treatment. These results suggest that a pretreatment with estradiol promoted dopamine neuron survival by activating ERalpha and increasing Akt and GSK3beta phosphorylation...

....

..The observation that ARs are present in axons and dendrites highlights the possibility that androgens play an important and novel extra-nuclear role in neuronal function...

..Thus, ERbeta and ERalpha may be required for E(2)'s modulation of affective and sexual behavior, respectively...

..These findings support the hypothesis of an early programming of the vulnerability to some neurological diseases during senescence and reinforce the potential therapeutic interest of IGF-1 during brain aging...

..Androgen receptors in axons located in the cerebral cortex and amygdala and originating in the hippocampus may play an important role in the rapid behavioral effects of androgens...

..In summary, our findings suggest that early postpartum period is associated with a modification of hippocampal function. This may reflect a homeostatic form of hippocampal plasticity in response to the onset of the maternal experience...

....

..Thus, both neurons and astrocytes in the male rat forebrain contain ARs, suggesting that androgens, via ARs, may exert effects on both cell types in an age- and region-dependent manner...