Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders.

Authors:
Dr. Marcia Ratner, PhD, DABT
Dr. Marcia Ratner, PhD, DABT
Department of Pharmacology and Experimental Therapeutics,Boston University School of Medicine
Project Manager
Toxicology, Neurology, Pharmacology
Boston, Massachusetts | United States

Front Endocrinol (Lausanne) 2019 9;10:169. Epub 2019 Apr 9.

Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, 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 (GABA), 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.

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http://dx.doi.org/10.3389/fendo.2019.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465949PMC

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April 2019
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