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Preclinical animal models of mental illnesses to translate findings from the bench to the bedside: Molecular brain mechanisms and peripheral biomarkers associated to early life stress or immune challenges

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@article{cd75876c546f407dab0df6a012223b8f,
title = "Preclinical animal models of mental illnesses to translate findings from the bench to the bedside: Molecular brain mechanisms and peripheral biomarkers associated to early life stress or immune challenges",
abstract = "Animal models are useful preclinical tools for studying the pathogenesis of mental disorders and the effectiveness of their treatment. While it is not possible to mimic all symptoms occurring in humans, it is however possible to investigate the behavioral, physiological and neuroanatomical alterations relevant for these complex disorders in controlled conditions and in genetically homogeneous populations. Stressful and infection-related exposures represent the most employed environmental risk factors able to trigger or to unmask a psychopathological phenotype in animals. Indeed, when occurring during sensitive periods of brain maturation, including pre, postnatal life and adolescence, they can affect the offspring's neurodevelopmental trajectories, increasing the risk for mental disorders. Not all stressed or immune challenged animals, however, develop behavioral alterations and preclinical animal models can explain differences between vulnerable or resilient phenotypes. Our review focuses on different paradigms of stress (prenatal stress, maternal separation, social isolation and social defeat stress) and immune challenges (immune activation in pregnancy) and investigates the subsequent alterations in several biological and behavioral domains at different time points of animals' life. It also discusses the {"}double-hit{"} hypothesis where an initial early adverse event can prime the response to a second negative challenge. Interestingly, stress and infections early in life induce the activation of the hypothalamic-pituitary-adrenal (HPA) axis, alter the levels of neurotransmitters, neurotrophins and pro-inflammatory cytokines and affect the functions of microglia and oxidative stress. In conclusion, animal models allow shedding light on the pathophysiology of human mental illnesses and discovering novel molecular drug targets for personalized treatments.",
keywords = "Adverse Childhood Experiences, Animals, Biomarkers, Brain, Disease Models, Animal, Female, Humans, Hypothalamo-Hypophyseal System, Maternal Deprivation, Mental Disorders/etiology, Pituitary-Adrenal System, Pregnancy, Prenatal Exposure Delayed Effects, Stress, Psychological",
author = "Nadia Cattane and Vernon, {Anthony C} and Alessandra Borsini and Catia Scassellati and Dominique Endres and Lucile Capuron and Ryad Tamouza and Benros, {Michael Eriksen} and Leza, {Juan C} and Pariante, {Carmine M} and Riva, {Marco A} and Annamaria Cattaneo and {European College of Neuropsychopharmacology (ECNP) ImmunoNeuroPsychiatry Thematic Working Group}",
note = "Copyright {\textcopyright} 2022. Published by Elsevier B.V.",
year = "2022",
month = may,
doi = "10.1016/j.euroneuro.2022.02.002",
language = "English",
volume = "58",
pages = "55--79",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Preclinical animal models of mental illnesses to translate findings from the bench to the bedside

T2 - Molecular brain mechanisms and peripheral biomarkers associated to early life stress or immune challenges

AU - Cattane, Nadia

AU - Vernon, Anthony C

AU - Borsini, Alessandra

AU - Scassellati, Catia

AU - Endres, Dominique

AU - Capuron, Lucile

AU - Tamouza, Ryad

AU - Benros, Michael Eriksen

AU - Leza, Juan C

AU - Pariante, Carmine M

AU - Riva, Marco A

AU - Cattaneo, Annamaria

AU - European College of Neuropsychopharmacology (ECNP) ImmunoNeuroPsychiatry Thematic Working Group

N1 - Copyright © 2022. Published by Elsevier B.V.

PY - 2022/5

Y1 - 2022/5

N2 - Animal models are useful preclinical tools for studying the pathogenesis of mental disorders and the effectiveness of their treatment. While it is not possible to mimic all symptoms occurring in humans, it is however possible to investigate the behavioral, physiological and neuroanatomical alterations relevant for these complex disorders in controlled conditions and in genetically homogeneous populations. Stressful and infection-related exposures represent the most employed environmental risk factors able to trigger or to unmask a psychopathological phenotype in animals. Indeed, when occurring during sensitive periods of brain maturation, including pre, postnatal life and adolescence, they can affect the offspring's neurodevelopmental trajectories, increasing the risk for mental disorders. Not all stressed or immune challenged animals, however, develop behavioral alterations and preclinical animal models can explain differences between vulnerable or resilient phenotypes. Our review focuses on different paradigms of stress (prenatal stress, maternal separation, social isolation and social defeat stress) and immune challenges (immune activation in pregnancy) and investigates the subsequent alterations in several biological and behavioral domains at different time points of animals' life. It also discusses the "double-hit" hypothesis where an initial early adverse event can prime the response to a second negative challenge. Interestingly, stress and infections early in life induce the activation of the hypothalamic-pituitary-adrenal (HPA) axis, alter the levels of neurotransmitters, neurotrophins and pro-inflammatory cytokines and affect the functions of microglia and oxidative stress. In conclusion, animal models allow shedding light on the pathophysiology of human mental illnesses and discovering novel molecular drug targets for personalized treatments.

AB - Animal models are useful preclinical tools for studying the pathogenesis of mental disorders and the effectiveness of their treatment. While it is not possible to mimic all symptoms occurring in humans, it is however possible to investigate the behavioral, physiological and neuroanatomical alterations relevant for these complex disorders in controlled conditions and in genetically homogeneous populations. Stressful and infection-related exposures represent the most employed environmental risk factors able to trigger or to unmask a psychopathological phenotype in animals. Indeed, when occurring during sensitive periods of brain maturation, including pre, postnatal life and adolescence, they can affect the offspring's neurodevelopmental trajectories, increasing the risk for mental disorders. Not all stressed or immune challenged animals, however, develop behavioral alterations and preclinical animal models can explain differences between vulnerable or resilient phenotypes. Our review focuses on different paradigms of stress (prenatal stress, maternal separation, social isolation and social defeat stress) and immune challenges (immune activation in pregnancy) and investigates the subsequent alterations in several biological and behavioral domains at different time points of animals' life. It also discusses the "double-hit" hypothesis where an initial early adverse event can prime the response to a second negative challenge. Interestingly, stress and infections early in life induce the activation of the hypothalamic-pituitary-adrenal (HPA) axis, alter the levels of neurotransmitters, neurotrophins and pro-inflammatory cytokines and affect the functions of microglia and oxidative stress. In conclusion, animal models allow shedding light on the pathophysiology of human mental illnesses and discovering novel molecular drug targets for personalized treatments.

KW - Adverse Childhood Experiences

KW - Animals

KW - Biomarkers

KW - Brain

KW - Disease Models, Animal

KW - Female

KW - Humans

KW - Hypothalamo-Hypophyseal System

KW - Maternal Deprivation

KW - Mental Disorders/etiology

KW - Pituitary-Adrenal System

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

KW - Stress, Psychological

UR - http://www.scopus.com/inward/record.url?scp=85125250440&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2022.02.002

DO - 10.1016/j.euroneuro.2022.02.002

M3 - Review

C2 - 35235897

VL - 58

SP - 55

EP - 79

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -

ID: 78243437