title: Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice.
abstract: Early life experiences play a key role in brain function and behaviour. Adverse events during childhood are therefore a risk factor for psychiatric disease during adulthood, such as mood disorders. Maternal separation is a validated mouse model for maternal neglect, producing negative early life experiences that result in subsequent emotional alteration. Mood disorders have been found to be associated with neurochemical changes and neurotransmitter deficits such as reduced availability of monoamines in discrete brain areas. Emotional alterations like depression result in reduced serotonin availability and enhanced kynurenine metabolism through the action of indoleamine 2, 3-dioxygenase in response to neuroinflammatory factors. This mechanism involves regulation of the neurotransmitter system by neuroinflammatory agents, linking mood regulation to neuroinmunological reactions. In this context, the aim of this study was to investigate the effects of maternal separation with early weaning on emotional behaviour in mice. We investigated neuroinflammatory responses and the state of the tryptophan-kynurenine metabolic pathway in discrete brain areas following maternal separation. We show that adverse events during early life increase risk of long-lasting emotional alterations during adolescence and adulthood. These emotional alterations are particularly severe in females. Behavioural impairments were associated with microglia activation and disturbed tryptophan-kynurenine metabolism in brain areas related to emotional control. This finding supports the preeminent role of neuroinflammation in emotional disorders.
authors.affiliation: Neurobiology of Behavior Research Group (GReNeC), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gracia-Rubio
authors.affiliation: Neurobiology of Behavior Research Group (GReNeC), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Moscoso-Castro
authors.affiliation: Bioanalysis Research Group, IMIM (Hospital del Mar Research Institute), Barcelona, Spain.
authors.forename: Oscar J
authors.initials: OJ
authors.lastname: Pozo
authors.affiliation: Bioanalysis Research Group, IMIM (Hospital del Mar Research Institute), Barcelona, Spain; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Marcos
authors.affiliation: Institut de Neurociències and Psychobiology Unit, Universitat Autònoma de Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Nadal
authors.affiliation: Neurobiology of Behavior Research Group (GReNeC), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; Neuroscience Research Program, IMIM (Hospital del Mar Research Institute) Barcelona, Spain. Electronic address: olga.valverde@upf.edu.
authors.forename: Olga
authors.initials: O
authors.lastname: Valverde
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001835:Body Weight; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D004644:Emotions / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008425:Maternal Behavior / Q000523:psychology; D008426:Maternal Deprivation; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology / Q000523:psychology; D011897:Random Allocation
chemical_list: D007737:Kynurenine
keywords: Despair behaviour; Early life experiences; Maternal neglect; Neuroinflammation; Tryptophan–kynurenine metabolism