Neurosteroids and Brain Function

This series offers the most comprehensive and up-to-date information available and is a must for anyone in the field.

Author: Ronald J. Bradley

Publisher: Academic Press

ISBN: 9780123668462

Category: Medical

Page: 513

View: 665

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

Neurosteroids and the Nervous System

​While steroids from the periphery have profound effects on the nervous system, the nervous system also produces its own steroids de novo (“neurosteroids”).

Author: Steven R. King

Publisher: Springer Science & Business Media

ISBN: 1461455596

Category: Medical

Page: 125

View: 160

​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.

New Perspectives in Neurosteroids action a Special Player Allopregnanolone

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 ...

Author: Valerio Magnaghi

Publisher: Frontiers Media SA

ISBN: 2889195554

Category:

Page:

View: 264

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.



Neurosteroids

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.

Author: Hubert Vaudry

Publisher: Frontiers E-books

ISBN: 2889190781

Category:

Page:

View: 659

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.

Neurosteroids

This book provides a comprehensive overview of the most exciting, late-breaking data in the neurosteroid field today, contributed by a pioneering panel of experts in the field.

Author: Taylor & Francis Group

Publisher:

ISBN: 9781482216233

Category:

Page:

View: 883


Neurosteroids

Neurosteroids and their precursors were employed along with compounds that prevented their activity at the GABAAR such as?-cyclodextrin, which is a barrel-shaped cyclic oligosaccharide with a lipophilic interior that sequesters ...

Author: Stephen R. Humble

Publisher:

ISBN:

Category:

Page:

View: 522

Peripheral sensitisation and central sensitisation are implicated in the development of neuropathic pain with neuroplasticity occurring at multiple levels of the pain pathway. Hypersensitivity of the spinothalamic tract has been described in neuropathic animal models of diabetes. Spinal dorsal horn neurones of diabetic rats exhibit abnormally high spontaneous firing, suggesting an imbalance between excitatory and inhibitory signals converging within this structure. GABAergic neurones within the spinal cord and thalamus are crucial for the transmission of painful stimuli to higher centres of the brain that are involved in pain perception. GABAA receptors (GABAARs) are an important target for many clinical drugs, and certain endogenous neurosteroids act as potent allosteric modulators of these receptors. A developmental change in the rate of exponential decay of GABAergic synaptic events has been observed in other types of neurones and this may be related in part to fluctuations in endogenous neurosteroid tone. The objective of this study was to investigate changes to inhibitory neurotransmission with development in three levels of the pain pathway and to explore potential mechanisms underlying diabetic neuropathy. The whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from wild type mice between the ages of 6 and 80 days in lamina II of the spinal cord, the nucleus reticularis (nRT) of the thalamus and the cerebral cortex. Recordings were also obtained from mice with diabetic neuropathy (ob/ob and db/db) between the ages of 60 and 80 days. Neurosteroids and their precursors were employed along with compounds that prevented their activity at the GABAAR such as ?-cyclodextrin, which is a barrel-shaped cyclic oligosaccharide with a lipophilic interior that sequesters neurosteroids. Behavioural experiments were also performed using von Frey filaments and the tail flick test to examine mechanical and thermal nociception. Recordings from the spinal cord, the thalamus and the cerebral cortex revealed that the decay time of miniature inhibitory postsynaptic currents are significantly reduced with development. The neurosteroids allopregnanolone and ganaxolone were significantly more effective in neurones from the older mice. In contrast, ?-cyclodextrin had significantly less effect in neurones from the older mice. In mature diabetic mice (ob/ob mice), the endogenous neurosteroid tone is reduced compared to control mice, but certain neurosteroid compounds have a greater effect on the GABAARs of these diabetic mice. In addition, the diabetic mice exhibit mechanical allodynia and hyperalgesia, which is responsive to exogenously applied neurosteroids. These results are consistent with the hypothesis that a dramatic reduction in endogenous neurosteroid tone occurs as development progresses and that this impacts on the exponential decay time of GABAergic mIPSCs within neurones of the pain pathway. The higher neurosteroid tone in the youngest mice may confer a degree of neural protection over the nervous system as it develops. The reduction of endogenous neurosteroid tone in diabetic mice may be associated with their hypersensitivity. It is possible that pregnane-derived neurosteroids may exert analgesic effects in pathological pain states by attempting to restore the physiological GABAergic inhibitory tone that is observed in immature animals.

Neurosteroids

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 ...

Author: Etienne-Emile Baulieu

Publisher: Humana Press

ISBN: 9781617370687

Category: Medical

Page: 378

View: 225

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.

Hormones Brain and Behavior Online

... Neurosteroids Function of Neurosteroids – Basic Research Function of Neurosteroids – Basic Research Behaviors Are Influenced by Neurosteroids Behaviors ...

Author:

Publisher: Academic Press

ISBN: 008088783X

Category: Medical

Page: 4393

View: 682

Hormones, Brain, and Behavior, Second Edition is a comprehensive work discussing the effect of hormones on the brain and, subsequently, behavior. This major reference work has 109 chapters covering a broad range of topics with an extensive discussion of the effects of hormones on insects, fish, amphibians, birds, rodents, and humans. To truly understand all aspects of our behavior, we must take every influence (including the hormonal influences) into consideration. Donald Pfaff and a number of well-qualified editors examine and discuss how we are influenced by hormonal factors, offering insight, and information on the lives of a variety of species. Hormones, Brain, and Behavior offers the reader comprehensive coverage of growing field of research, with a state-of-the-art overview of hormonally-mediated behaviors. This reference provides unique treatment of all major vertebrate and invertebrate model systems with excellent opportunities for relating behavior to molecular genetics. The topics cover an unusual breadth (from molecules to ecophysiology), ranging from basic science to clinical research, making this reference of interest to a broad range of scientists in a variety of fields. Available online exclusively via ScienceDirect. A limited edition print version is also available. Comprehensive coverage of a growing field of research Unique treatment of all major vertebrate and invertebrate model systems with excellent opportunites for relating behavior to molecular genetics Covers an unusual breadth ranging from molecules to ecophysiology, and from basic science to clinical research



Neurosteroid Effects in the Central Nervous System

4.5 EFFECTS OF NEUROSTEROIDS ON αβδ RECEPTOR CURRENTS Although an early study suggested that the δ subunit conferred a novel resistance to positive ...

Author: Sheryl S. Smith

Publisher: CRC Press

ISBN: 9780203508169

Category: Medical

Page: 408

View: 226

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,

Neurosteroids

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 ...

Author: Michael Schumacher (MD.)

Publisher:

ISBN:

Category: Neuroendocrinology

Page: 378

View: 346

"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."--Publisher description (LoC).


Investigation of Two Interacting Neurosteroid Sites on a GABA Receptor by Mutagenesis and Mathematical Modeling

This contributes to an expanded understanding of the allosteric regulatory pathways of GABA receptors and has provided a lead-in toward drug development by adding to the characterization of a potentially useful site for the development of ...

Author: Lindsay A. Horn

Publisher:

ISBN:

Category: GABA

Page: 136

View: 488

Given the utility of GABA receptor ligands as anthelminthics and insecticides, further study of invertebrate GABA receptor modulation promises to help identify new drugs to combat emerging resistance. The C. elegans GABA receptor, UNC-49, is modulated by the neurosteroids pregnenolone sulfate and pregnanolone, identifying neurosteroids as potential lead compounds. Notably, neurosteroid sites are non-conserved between invertebrates and mammals, limiting possible cross-toxicity. This proposal is focused on better understanding neurosteroid modulation of UNC-49. In several UNC-49 mutants, pregnanolone and sulfated neurosteroids serve as positive allosteric regulators suggesting neurosteroids may activate inhibitory and enhancing pathways simultaneously which contribute to an overall additive effect on the receptor. Our hypothesis is that there are two pathways operating separately and independently: a novel inhibitory pathway acting negatively, and the well-recognized enhancement pathway acting purely positively. To test this hypothesis, we used data from a receptor mutation, M2 15', designed to increase efficiency of the enhancing pathway and observed the difference to the balance between inhibition and enhancement. M2 15' is a universal positive allosteric residue known for involvement in enhancement of GABA receptors by many modulators. We mathematically modeled the data to attribute the change in modulation caused by the mutation solely to a change in enhancement. The experiment was performed on multiple receptor chimeras to confirm wider applicability of the model. Because M2 15' is known as an enhancing residue, we predict that changes in modulation will be attributable solely to increased activity of the enhancement pathway, thus confirming that enhancement is operating independently of and simultaneously with inhibition. Receptors showed decreased inhibition and/or increased enhancement when exposed to the neurosteroids consistent with multiple pathways occurring. However, unexpectedly, the mutations to the enhancement pathway also affected the activity of the inhibition pathway. These data suggest M2 15' is not involved solely in enhancement and may be involved in neurosteroid inhibition. This reveals a new function for well-studied M2 15' as a residue involved in both inhibition and enhancement. In addition, modeling suggests that the neurosteroid directly affects the gating process rather than affecting the process that occurs between ligand binding and channel opening. This narrows down the set of receptor conformational changes that may be allosterically inhibited by neurosteroids. This contributes to an expanded understanding of the allosteric regulatory pathways of GABA receptors and has provided a lead-in toward drug development by adding to the characterization of a potentially useful site for the development of novel pesticides.

Neuroactive Steroids in Brain Function Behavior and Neuropsychiatric Disorders

rats.22 This effect was similar to the effect observed following co-administration of NMDA and the NMDA antagonist D-AP5.22 Again, the 3β-OH neurosteroids ...

Author: Abraham Weizman

Publisher: Springer Science & Business Media

ISBN: 9781402068546

Category: Medical

Page: 564

View: 811

This book provides an up-to-date overview of the role of neurosteroids and neuroactive steroids in the regulation of brain processes and neuropsychiatric disorders. It addresses the neurosteroid function in brain development and plasticity, in both the normal and the pathological brain. It also suggests possible therapeutic approaches to the use of natural occurring or sinthetic neurosteroids. The contributors suggest that neuroactive steroids could have a role in clinical practice.