Cargando…

Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone

Post-traumatic stress disorder (PTSD) is a debilitating undertreated condition that affects 8%–13% of the general population and 20%–30% of military personnel. Currently, there are no specific medications that reduce PTSD symptoms or biomarkers that facilitate diagnosis, inform treatment selection o...

Descripción completa

Detalles Bibliográficos
Autor principal: Pinna, Graziano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579844/
https://www.ncbi.nlm.nih.gov/pubmed/31244621
http://dx.doi.org/10.3389/fnbeh.2019.00114
_version_ 1783427915196661760
author Pinna, Graziano
author_facet Pinna, Graziano
author_sort Pinna, Graziano
collection PubMed
description Post-traumatic stress disorder (PTSD) is a debilitating undertreated condition that affects 8%–13% of the general population and 20%–30% of military personnel. Currently, there are no specific medications that reduce PTSD symptoms or biomarkers that facilitate diagnosis, inform treatment selection or allow monitoring drug efficacy. PTSD animal models rely on stress-induced behavioral deficits that only partially reproduce PTSD neurobiology. PTSD heterogeneity, including comorbidity and symptoms overlap with other mental disorders, makes this attempt even more complicated. Allopregnanolone, a neurosteroid that positively, potently and allosterically modulates GABA(A) receptors and, by this mechanism, regulates emotional behaviors, is mainly synthesized in brain corticolimbic glutamatergic neurons. In PTSD patients, allopregnanolone down-regulation correlates with increased PTSD re-experiencing and comorbid depressive symptoms, CAPS-IV scores and Simms dysphoria cluster scores. In PTSD rodent models, including the socially isolated mouse, decrease in corticolimbic allopregnanolone biosynthesis is associated with enhanced contextual fear memory and impaired fear extinction. Allopregnanolone, its analogs or agents that stimulate its synthesis offer treatment approaches for facilitating fear extinction and, in general, for neuropsychopathologies characterized by a neurosteroid biosynthesis downregulation. The socially isolated mouse model reproduces several other deficits previously observed in PTSD patients, including altered GABA(A) receptor subunit subtypes and lack of benzodiazepines pharmacological efficacy. Transdiagnostic behavioral features, including expression of anxiety-like behavior, increased aggression, a behavioral component to reproduce behavioral traits of suicidal behavior in humans, as well as alcohol consumption are heightened in socially isolated rodents. Potentials for assessing novel biomarkers to predict, diagnose, and treat PTSD more efficiently are discussed in view of developing a precision medicine for improved PTSD pharmacological treatments.
format Online
Article
Text
id pubmed-6579844
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-65798442019-06-26 Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone Pinna, Graziano Front Behav Neurosci Neuroscience Post-traumatic stress disorder (PTSD) is a debilitating undertreated condition that affects 8%–13% of the general population and 20%–30% of military personnel. Currently, there are no specific medications that reduce PTSD symptoms or biomarkers that facilitate diagnosis, inform treatment selection or allow monitoring drug efficacy. PTSD animal models rely on stress-induced behavioral deficits that only partially reproduce PTSD neurobiology. PTSD heterogeneity, including comorbidity and symptoms overlap with other mental disorders, makes this attempt even more complicated. Allopregnanolone, a neurosteroid that positively, potently and allosterically modulates GABA(A) receptors and, by this mechanism, regulates emotional behaviors, is mainly synthesized in brain corticolimbic glutamatergic neurons. In PTSD patients, allopregnanolone down-regulation correlates with increased PTSD re-experiencing and comorbid depressive symptoms, CAPS-IV scores and Simms dysphoria cluster scores. In PTSD rodent models, including the socially isolated mouse, decrease in corticolimbic allopregnanolone biosynthesis is associated with enhanced contextual fear memory and impaired fear extinction. Allopregnanolone, its analogs or agents that stimulate its synthesis offer treatment approaches for facilitating fear extinction and, in general, for neuropsychopathologies characterized by a neurosteroid biosynthesis downregulation. The socially isolated mouse model reproduces several other deficits previously observed in PTSD patients, including altered GABA(A) receptor subunit subtypes and lack of benzodiazepines pharmacological efficacy. Transdiagnostic behavioral features, including expression of anxiety-like behavior, increased aggression, a behavioral component to reproduce behavioral traits of suicidal behavior in humans, as well as alcohol consumption are heightened in socially isolated rodents. Potentials for assessing novel biomarkers to predict, diagnose, and treat PTSD more efficiently are discussed in view of developing a precision medicine for improved PTSD pharmacological treatments. Frontiers Media S.A. 2019-06-11 /pmc/articles/PMC6579844/ /pubmed/31244621 http://dx.doi.org/10.3389/fnbeh.2019.00114 Text en Copyright © 2019 Pinna. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Neuroscience
Pinna, Graziano
Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone
title Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone
title_full Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone
title_fullStr Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone
title_full_unstemmed Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone
title_short Animal Models of PTSD: The Socially Isolated Mouse and the Biomarker Role of Allopregnanolone
title_sort animal models of ptsd: the socially isolated mouse and the biomarker role of allopregnanolone
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579844/
https://www.ncbi.nlm.nih.gov/pubmed/31244621
http://dx.doi.org/10.3389/fnbeh.2019.00114
work_keys_str_mv AT pinnagraziano animalmodelsofptsdthesociallyisolatedmouseandthebiomarkerroleofallopregnanolone