How can one class of compounds have so many potential applications? The answer may lie in the ability of neuroactive steroids to regulate synaptic and extrasynaptic inhibitory transmission across brain, hypothalamic-pituitary-adrenal (HPA) axis function, inflammatory processes and myelin formation.
Neuroactive steroids modulate CNS development and repair following injury
The neurodevelopmental functions and mechanisms of action of four distinct neurosteroids – pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone are reviewed by Mellon (this issue). Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity.
Progesterone and its metabolites also promote the viability of neurons in the adult brain and spinal cord….Thus, the hormone may promote neuroregeneration by several different actions: by reducing inflammation, swelling and apoptosis, thereby increasing the survival of neurons, and by promoting the formation of new myelin sheaths. Recognition of the important pleiotropic effects of progesterone supports the therapeutic potential for the treatment of brain lesions and other diseases of the nervous system.
Neuroactive steroids modulate the HPA axis and the effects of stressThe ability of neuroactive steroids to reduce HPA axis activation may play an important role in returning the animal to homeostasis following stressful events.
whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability.
Summary and Conclusions
….there is great optimism in the field for the usefulness of the inhibitory, anti-inflammatory, and myelin promoting targets of neuroactive steroids for CNS disease.
Longing4Cheese wrote: I will be happy to attempt a recap of the MS Roundtable later; right now I have to run around and do some errands. The short version is that the lineup included lots of accomplished neurologist-researchers, but the one I was most looking forward to speaking with, Dr. Dennis Bourdette of Oregon Health Sciences University (where he holds, among other things, a chair named for Dr. Swank) was not in attendance.
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