New Perspectives In Neurosteroids Action A Special Player Allopregnanolone

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.

Fluoxetine, best known by the trade name Prozac®, unlike other psychotropic drugs whose effects were serendipitously stumbled upon, was the first developed for a precise mechanism of action, that is, the ability to selectively inhibit serotonin reuptake, based upon the theory that increasing the availability of serotonin would treat major depression. Once approved by the FDA in 1987, fluoxetine quickly became the most prescribed psychotropic drug worldwide and its success in improving mood disorders has triggered the development of a large number of congener molecules, commonly known as SSRIs after their purported mechanism of action. However, a quarter of a century after its development, the idea that fluoxetine asserts its positive behavioral effect through inhibition of serotonergic reuptake is not firmly established. This book reviews several preclinical and clinical reports suggesting that the pharmacological effects of fluoxetine may be mediated by means other than the regulation of serotonin, including the regulation of gene expression, modifying epigenetic mechanisms as well as modifying microRNAs. One of the most prominent mechanisms for the therapeutic relevance of fluoxetine relates to influencing neuroplasticity by enhancing neurotropic factors, including BDNF signaling and altering adult neurogenesis. The ability of fluoxetine to rapidly increase neurosteroid levels accounts for the fast anxiolytic effects of this drug. Fluoxetine action at sigma-1 receptor or modulating glutamatergic neurotransmission as well as the combination of fluoxetine with other psychotropic drugs is discussed in relation to its therapeutic effects. While fluoxetine was primarily prescribed as an antidepressant, this drug currently represents a treatment of choice for a broad spectrum of psychiatric disorders, including post-traumatic stress disorder and a range of anxiety disorders. This drug even possesses analgesic actions and is a valuable therapy for stroke. This book also highlights emerging evidence on the gender-specific effects of fluoxetine, its potential adverse features, including its addiction liability in combination with psychostimulants, and the impact of perinatal fluoxetine exposure.

Sex Differences in the Central Nervous System offers a comprehensive examination of the current state of sex differences research, from both the basic science and clinical research perspectives. Given the current NIH directive that funded preclinical research must consider both females and males, this topic is of interest to an increasing percentage of the neuroscience research population. The volume serves as an invaluable resource, offering coverage of a wide range of topics: sex differences in cognition, learning, and memory, sex hormone signaling mechanisms, neuroimmune interactions, epigenetics, social behavior, neurologic disease, psychological disorders, and stress. Discussions of research in both animal models and human patient populations are included. Details how sex hormones have widespread effects on the nervous system and influence the way males and females function Assists readers in determining how sex impacts their research and practice, and assists in determining how to adjust research programs to incorporate sex influences Includes discussions of research in both animal models and human patient populations, and at various developmental stages Features revised and updated chapters by leaders in the field around the globe—the broadest, most expert coverage available

With recent studies using genetic, epigenetic, and other molecular and neurochemical approaches, a new era has begun in understanding pathophysiology of suicide. Emerging evidence suggests that neurobiological factors are not only critical in providing potential risk factors but also provide a promising approach to develop more effective treatment and prevention strategies. The Neurobiological Basis of Suicide discusses the most recent findings in suicide neurobiology. Psychological, psychosocial, and cultural factors are important in determining the risk factors for suicide; however, they offer weak prediction and can be of little clinical use. Interestingly, cognitive characteristics are different among depressed suicidal and depressed nonsuicidal subjects, and could be involved in the development of suicidal behavior. The characterization of the neurobiological basis of suicide is in delineating the risk factors associated with suicide. The Neurobiological Basis of Suicide focuses on how and why these neurobiological factors are crucial in the pathogenic mechanisms of suicidal behavior and how these findings can be transformed into potential therapeutic applications.

The Human Hypothalamus: Neuropsychiatric Disorders, Volume 181 in the Handbook of Clinical Neurology series, provides comprehensive summaries of recent research on the brain and nervous system as they relate to clinical neurology. This volume identifies the neurobiology and neurophysiology of disorders relating to the hypothalamus and provides treatment information for these disorders. Disorders covered include neuropsychiatric, neurodegenerative, periodic, and autoimmune disorders. Coverage includes Alzheimer’s, Parkinson’s, epilepsy, sleep, pain, depression, anxiety, OCD, PTSD, schizophrenia, autism, aggressions, addiction, and more. Summarizes research on how the hypothalamus relates to neurological disorders Contains neuropsychiatric, neurodegenerative, periodic and autonomic disorders Includes the neurobiology of, and treatment for, each disorder Covers depression, anxiety, OCD, PTSD, schizophrenia, autism, aggression, addiction, and more Provides coverage of sleep and pain

The book provides chapters on sex hormones and their modulation in neurodegenerative processes and pathologies, from basic molecular mechanisms, physiology, gender differences, to neuroprotection and clinical aspects for potential novel pharmacotherapy approaches. The book contains 14 chapters written by authors from various biomedical professions, from basic researchers in biology and physiology to medicine and veterinary medicine, pharmacologists, psychiatrist, etc. Chapters sum up the past and current knowledge on sex hormones, representing original new insights into their role in brain functioning, mental disorders and neurodegenerative diseases. The book is written for a broad range of audience, from biomedical students to highly profiled medical specialists and biomedical researchers, helping them to expand their knowledge on sex hormones in neurodegenerative processes and opening new questions for further investigation.

Anesthesia and Analgesia in Laboratory Animals focuses on the special anesthetic, analgesic, and postoperative care requirements associated with experimental surgery. Fully revised and updated this new edition provides the reader with agents, methods, and techniques for anesthesia and analgesia that ensure humane and successful procedural outcomes. * Provides researchers with the most comprehensive and up-to-date review of the use of anesthesia and analgesia in laboratory animals * Thoroughly updated with new material on ferrets, birds, reptiles, amphibians, fish, and invertebrates * Includes hot topic areas such as pain research, ethical issues, legal issues, and imaging studies