ReviewGlia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones
Section snippets
Introduction: Neuroprotective effects of sex hormones
By the middle of XIX century, Berthold had already demonstrated [21] that the brain is a target for gonadal secretions. Later, after the identification of the molecular structure of gonadal hormones, specific neural events that were affected by sex steroids were recognized. These included the process of sexual differentiation of the brain and spinal cord and the regulation of neuroendocrine events and sex behaviors [35], [81], [122]. However, in the last 15 years, it has become evident that sex
Production of steroids by neurons and glia
Sex steroids may exert a broad set of actions in the nervous system because these molecules have the distinction of being peripherally produced hormones as well as locally produced neuromodulators. The interaction between steroid hormones and steroids produced locally by neural tissue is far from being completely understood. Both the central and the peripheral neural tissues have the capability to synthesize steroids from cholesterol and to metabolize steroid hormones. Proteins involved in the
Sex hormone receptors in glia
Sex hormone receptors are expressed in the CNS, both in neurons and in non-neuronal cells. Estrogen receptors (ERs), androgen receptor (AR) and progesterone receptor (PR) expression has also been described in glial cells of the CNS, in vitro and in vivo, under normal and/or neurodegenerative conditions, as summarized in Table 1. In addition, Schwann cells and astrocytes express the GABAA receptor and consequently may respond to steroids that interact with this neurotransmitter receptor, such as
Microglia
The well-known anti-inflammatory effects of sex steroids in peripheral tissues have been also observed in the brain. Steroids exert their anti-inflammatory actions in the brain by acting on non-neuronal cells, mainly on microglia. Microglial cells, like macrophages, are targets for some steroids. In general, steroids induce an inhibition of inflammatory responses in both cell types. Steroids such as dehydroepiandrosterone and progesterone, inhibit nitric oxide production in primary cultures of
Concluding remarks
Neural insults induce numerous protective and reparative responses. To be most effective, these responses should be well-coordinated and redundant, should be induced rapidly, and sustained as long as necessary, should not impair normal neuronal functioning nor disrupt established pathways, should allow the cells most affected to temporarily shift function to sustaining survival, and should not adversely affect the physiology of the rest of the organism except when sickness behaviors would speed
Note added in proof
Chaban et al. [34] have recently reported the existence of estrogen receptors in the plasma membrane of astrocytes. Sortino et al. [178] have proved that conditioned media from estradiol-stimulated astrocytes protects neuronal cultures from beta-amyloid toxicity. Finally, Takahashi et al. [187] have detected the expression of estrogen receptor-β in microglia/macrophages in the brain of postischemic monkeys.
Acknowledgments
We acknowledge support from the Ministerio de Ciencia y Tecnología (SAF 2002-00652), Commission of the European Communities, specific RTD programme “Quality of life and management of living resources’’, QLK6-CT-2000-00179 and USPHS MH 62588.
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