The Role of Neuroactive Steroids in Learning and Memory Deficits Associated with Neurologic and Neuropsychiatric Disorders.

Marcia H Ratner, Vidhya Kumaresan, David H Farb

Overview

Memory dysfunction is a well recognized clinical manifestation of many neurologic and neuropsychiatric disorders. However, the role of endogenous neurosteroids in these deficits has not been fully elucidated. We review the literature on this topic and provide a path forward for future research in this area. We also discuss the potential role of synthetic neuroactive steroids as therapeutics for these memory deficits.

Summary

This review explores the effects of endogenous and exogenously administered neuroactive steroids on neural networks across the life span in men and women. We synthesize the body of peer reviewed literature to reveal the unique and common pathways via which these naturally occurring neuromodulators alter memory function in normal subjects and in persons with neurologic and neuropsychiatric disorders. We discuss the potential role of using synthetic analogues of these neurosteroids as therapeutics for memory disorders.

Author Comments

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
Writing this article with my co-authors with whom I have long standing collaborations was a great pleasure.Dr. Marcia Ratner, PhD, DABT

Resources

Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders
https://www.frontiersin.org/articles/10.3389/fendo.2019.00169/full

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.

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2019.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465949PMC
April 2019
34 Reads

Publication Analysis

Top Keywords

circuitry function
8
altered states
8
disorders memory
8
memory
7
exogenously administered
4
neurosteroid allosteric
4
negative neurosteroid
4
gaba nmda
4
administered neurosteroids
4
neurodegenerative disorders
4
positive negative
4
allosteric modulators
4
gaba type-a
4
type-a gaba
4
active exogenously
4
discovery positive
4
modulators gaba
4
aggregating multiple
4
advances leading
4
age-related neurodegenerative
4

References

(Supplied by CrossRef)
Isolation and properties of porcine thyrotropin-releasing hormone
Schally et al.
J Biol Chem. 1969
Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P
Chang et al.
J Biol Chem. 1970
Pregnenolone and its sulfate ester in the rat brain
Corp├ęchot et al.
Brain Res. 1983
Neurosteroids: pregnenolone in human sciatic nerves
Morfin et al.
Proc Natl Acad Sci USA. 1992
Anaesthetic effects of steroid hormones
Selye et al.
Proc Soc Exp Biol Med. 1941

Similar Publications