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
European Neuropsychopharmacology. 2022-05-01; 58: 55-79
DOI: 10.1016/j.euroneuro.2022.02.002
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1. Eur Neuropsychopharmacol. 2022 May;58:55-79. doi:
10.1016/j.euroneuro.2022.02.002. Epub 2022 Feb 27.
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.
Cattane N(1), Vernon AC(2), Borsini A(3), Scassellati C(1), Endres D(4), Capuron
L(5), Tamouza R(6), Benros ME(7), Leza JC(8), Pariante CM(3), Riva MA(9),
Cattaneo A(10); European College of Neuropsychopharmacology (ECNP)
ImmunoNeuroPsychiatry Thematic Working Group.
Author information:
(1)Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio
Fatebenefratelli, Brescia, Italy.
(2)Department of Basic and Clinical Neuroscience, Institute of Psychiatry,
Psychology and Neuroscience, King’s College London, United Kingdom; MRC Centre
for Neurodevelopmental Disorders, King’s College London, United Kingdom.
(3)Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry,
Psychology and Neuroscience, Department of Psychological Medicine, King’s
College London, United Kingdom.
(4)Department of Psychiatry and Psychotherapy, Medical Center-University of
Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
(5)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux,
France.
(6)Département Medico-Universitaire de Psychiatrie et d’Addictologie (DMU
ADAPT), Laboratoire Neuro-psychiatrie translationnelle, AP-HP, UniversitéParis
Est Créteil, INSERM U955, IMRB, Hôpital Henri Mondor, Fondation FondaMental,
F-94010 Créteil, France.
(7)Biological and Precision Psychiatry, Copenhagen Research Centre for Mental
Health, Copenhagen University Hospital, Gentofte Hospitalsvej 15, 4th floor,
2900 Hellerup, Denmark; Department of Immunology and Microbiology, Faculty of
Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200
Copenhagen N, Denmark.
(8)Department of Pharmacology & Toxicology, Faculty of Medicine, Universidad
Complutense de Madrid (UCM), Centro de Investigación Biomédica en Red de Salud
Mental (CIBERSAM), Instituto de Investigación Hospital 12 de Octubre (i+12),
IUIN-UCM. Spain.
(9)Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio
Fatebenefratelli, Brescia, Italy; Department of Pharmacological and Biomolecular
Sciences, University of Milan, Italy.
(10)Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio
Fatebenefratelli, Brescia, Italy; Department of Pharmacological and Biomolecular
Sciences, University of Milan, Italy. Electronic address:
.
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.
Copyright © 2022. Published by Elsevier B.V.
DOI: 10.1016/j.euroneuro.2022.02.002
PMID: 35235897 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of Competing Interest C.M.P. has
received research funding from Johnson & Johnson for research on depression and
inflammation, and from the Wellcome Trust strategy award to the Neuroimmunology
of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium (104,025), which is
also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer. M.A.R. has
received compensation as speaker/consultant from Angelini, Iqvia, Lundbeck,
Otzuka, Sumitomo Dainippon Pharma and Sunovion. JCL has received compensation as
speaker/consultant from Janssen, Lundbeck and Sanofi. However, this paper is
independent from these funds. All other authors declare no conflict of interest.