Steroids and neuroprotection: New advances

Abstract

Gonadal hormones exert neuroprotective actions. In addition, it has become evident that the local synthesis of these molecules in the central nervous system may prevent or reduce neurodegeneration.The neuroprotective actions of steroids involve neurons, glial cells and blood vessels, are exerted via steroid receptor signaling initiated at the nuclear or membrane level and steroid receptor independent mechanisms. They include the regulation of phosphatases and kinases and the regulation of the expression of molecules controlling inflammation and apoptosis. In addition, mitochondria have emerged as new central targets for neuroprotective actions of steroids. These neuroprotective actions have been documented in different experimental models of neurological alterations, including motoneuron injury, Parkinson's disease, traumatic brain injury, multiple sclerosis, stroke and Alzheimer's disease. In addition, steroids promote serotonergic neuronal function and protect against affective disorders. 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

Fig. 1

Multiple neuroprotective mechanisms of steroids. Steroid brain concentrations depend of both their systemic levels and their local synthesis and metabolism. Steroids activate in the brain both steroid receptor dependent and steroid receptor independent mechanisms that involve the cell nucleus, the plasma membrane and the mitochondria. By these mechanisms, steroids regulate the transcription of genes involved in the control of neuronal survival, decrease excitotoxicity and exert anti-oxidant effects.

Fig. 2

Besides promoting neuronal survival by a direct action on neurons, steroids also exert complementary and interrelated actions that result in the reduction of brain damage and in the repair of the injured brain tissue. Steroids reduce reactive gliosis and inflammation, promote the remyelination of injured axons, control the function of the neurovascular unit, reduce brain edema, and promote neurogenesis in the injured brain.