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 - European College of Neuropsychopharmacology (ECNP) ImmunoNeuroPsychiatry Thematic Working Group
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
N1 - Funding Information:
M.A.R. has received research grants from Lundbeck, Sumitomo Dainippon Pharma and Sunovion.
Funding Information:
N.C., C.S. and A.C. have received funding from Ricerca Corrente (Italian Ministry of Health, MoH). A.C. has been also supported by PSR. A.C.V. has received funding from the Medical Research Council UK (grant No. MR/N025377/1 and Center grant MR/N026063/1). A.B. has received research funding by the Medical Research Council UK (grant No. MR/N029488/1) and by the National Institute for Health Research (NIHR) Biomedical Research center at South London and Maudsley NHS Foundation Trust and King's College London. She has also received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement N 848,158. C.M.P. was funded by the UK National Institute for Health Research (NIHR) Biomedical Research center at the South London and Maudsley NHS Foundation Trust and King's College London, the UK Medical Research Council (grants No. MR/L014815/1, MR/J002739/1 and MR/N029488/1) and the Psychiatry Research Trust. J.C.L.'s group has received competitive research funding from MCINN and FIS-ISCIII Ministries Spain (grants: PID2019-109033RB-I00,SAF 2016/75500-R, CIBERSAM-G12).
Publisher Copyright:
© 2022
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.
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 - Article
C2 - 35235897
SN - 0924-977X
VL - 58
SP - 55
EP - 79
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -
