Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders
- 1Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, School of Medicine, Boston University, United States
- 2Boston University, United States
Memory dysfunction is a symptomatic feature of many neurologic and neuropsychiatric disorders; however, the basic underlying mechanisms of memory and altered states of circuitry function associated with disorders of memory remain a vast unexplored territory. The initial discovery of endogenous neurosteroids triggered a quest to elucidate their role as neuromodulators in normal and diseased brain function. In this review, based on the perspective of our own research, the advances leading to the discovery of positive and negative neurosteroid allosteric modulators of GABA type-A (GABAA), NMDA, and non-NMDA type glutamate receptors are brought together in a historical and conceptual framework. We extend the analysis toward a state-of-the art view of how neurosteroid modulation of neural circuitry function may affect memory and memory deficits. By aggregating the results from multiple laboratories using both animal models for disease and human clinical research on neuropsychiatric and age-related neurodegenerative disorders, elements of a circuitry level view begins to emerge. Lastly, the effects of both endogenously active and exogenously administered neurosteroids on neural networks across the life span of women and men point to a possible underlying pharmacological connectome by which these neuromodulators might act to modulate memory across diverse altered states of mind.
Keywords: neurosteroid, Memory, Anxiety, Depression, Schizophrenia, Allopregnanolone, pregnenolone sulfate, Pregnenolone, Allopregnanolone (3α,5α-THP), Alzheimer's disease
Received: 24 Aug 2018;
Accepted: 28 Feb 2019.
Edited by:Vance L. Trudeau, University of Ottawa, Canada
Reviewed by:David Vaudry, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Xavier Xifró, University of Girona, Spain
Copyright: © 2019 Ratner, Kumaresan and Farb. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. David H. Farb, Boston University, Boston, United States, email@example.com