Neurosteroids

International Review of Neurobiology, Volume 46 presents in-depth reviews on such ground-breaking topics as assembly and intracellular trafficking of GABA A receptors, D-1 dopamine receptors, and Alzheimer's disease. This series offers the most comprehensive and up-to-date information available and is a must for anyone in the field. Includes a historical overview of neurosteroid research Contains a chapter on neurosteroid biosynthesis and regulation Presents current methods of neurosteroid measurement and analysis Discusses neurosteroid function in both the normal and the pathological brain Chapters address the function of neurosteroid in: Stress, Receptor plasticity and function, Learning and Memory, Alcohol use, Depression

Our understanding of the ways that neuroactive steroids act in the brain has been increased by transgenic approaches, recombinant expression systems, higher resolution electrophysiological paradigms, and the development of technology to localize receptors. Recent behavioral studies examining the effects of steroids on mood, seizure susceptibility,

​While steroids from the periphery have profound effects on the nervous system, the nervous system also produces its own steroids de novo (“neurosteroids”). The physiological importance of neurosteroids is beginning to be understood. These steroids potentially have roles in sedative/hypnotic behavior, anxiety, learning, and memory. At the cellular level, neurosteroids affect neuronal excitability, synaptic plasticity and cell proliferation and survival. Early findings hold promise for future strategies to treat specific psychologicalconditions and neurological diseases. This Brief will focus on the current state of understanding of brainderived neurosteroids.

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the development of new diagnostic and therapeutic approaches has been disappointingly slow. Translational Research in Traumatic Brain Injury attempts to integrate expertise from across specialties to address knowledge gaps in the field of TBI. Its chapters cover a wide scope of TBI research in five broad areas: Epidemiology Pathophysiology Diagnosis Current treatment strategies and sequelae Future therapies Specific topics discussed include the societal impact of TBI in both the civilian and military populations, neurobiology and molecular mechanisms of axonal and neuronal injury, biomarkers of traumatic brain injury and their relationship to pathology, neuroplasticity after TBI, neuroprotective and neurorestorative therapy, advanced neuroimaging of mild TBI, neurocognitive and psychiatric symptoms following mild TBI, sports-related TBI, epilepsy and PTSD following TBI, and more. The book integrates the perspectives of experts across disciplines to assist in the translation of new ideas to clinical practice and ultimately to improve the care of the brain injured patient.

Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.

Thirty years ago, the group of Baulieu and colleagues discovered that certain steroid hormones were present in higher amounts in the brain than in the plasma, and also found that suppression of circulating steroids by adrenalectomy and castration did not affect the concentration of pregnenolone, dehydroepiandrosterone and their sulfate esters in the rat brain. These seminal observations led to the concept that the brain, in very much the same way as the adrenal cortex, testis, ovary and placenta, was capable of synthesizing steroids. These brain born steroids, called neurosteroids, have been found to exert a vast array of biological activities. A number of steroidogenic enzymes have now been identified in the central nervous system by immunohistochemistry and in situ hybridization, and the neuronal and hormonal mechanisms regulating the biosynthesis of neurosteroids have been partially elucidated. The aim of this Research Topic is to celebrate three decades of research on neurosteroids by gathering a bouquet of review papers and original articles from leading scientists in the flourishing field of neurosteroids.

Etienne-Emile Baulieu, the discoverer of neurosteroids, and a panel of distinguished scientists and clinical researchers exhaustively and critically review all facets of neurosteroids involved in behavior, stress, memory, depression, anxiety, aging of the brain, and neurodegenerative diseases. These contributors illuminate the role of neurosteroids in brain development and plasticity and detail their neuromodulatory influence on GABAA, ionotropic glutamate receptors, acetylcholine receptors, sigma receptors, and calcium channels. Clearly pointing the way toward novel pharmaceutical agents that may be of significant therapeutic value, particularly with regard to aging mental functions, Neurosteroids: A New Regulatory Function in the Nervous System offers neurobiologists, psychiatrists, neurosurgeons, pharmacologists, and geriatricians the first comprehensive, state-of-the-art review of these important bioactive molecules.

Early in the 80’s date the first observations on the existence of hormonal steroids that may be synthesized and act in the nervous system. In order to refer to these endogenous steroids, proved important to control both central and peripheral nervous system, it was proposed the term “neurosteroids” (NSs). Over the years, their importance in regulating the physiological functions of neuronal and glial cells increased progressively. These steroids can be involved in several pathophysiological conditions such as depression, anxiety, premenstrual syndrome (PMS), schizophrenia and Alzheimer disease. Among the different classes of NSs, the progestagens revealed particularly important. The progesterone metabolite 5a-pregnan-3a-ol-20-one, also named tetrahydroprogesterone or allopregnanolone (ALLO) was one of the first most important steroid that was originally shown to act as neurosteroid. ALLO is synthesized through the action of the 5aR-3a-HSD, which converts P into DHP and subsequently, via a bidirectional reaction, into ALLO. NSs exert complex effects in the nervous system through ‘classic’, genomic, and ‘non-classic’, non-genomic actions. ALLO displays a rapid ‘non-genomic’ effect, which mainly involves the potent modulation of the GABA type A (GABA-A) receptor function. Recently a membrane receptor has been identified as target for ALLO effects, i.e. the membrane progesterone receptors (mPRs) that are able to activate a signalling cascade through G protein dependent mechanisms. By these ways, ALLO is able to modulate several cell functions, acting as neurogenic molecule on neural progenitor cells, as well as by activating proliferation and differentiation of glial cells in the central and peripheral nervous system. In this topic, we review the most recent acquisitions in the field of neurosteroids, focusing our attention on ALLO because its effects on the physiology of neurons and glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues and for the treatment of neuropsychiatric disorders.