title: Exposure to early life stress regulates Bdnf expression in SERT mutant rats in an anatomically selective fashion.
abstract: Although the causes of psychiatric disorders are not fully understood, it is well established that mental illness originates from the interaction between genetic and environmental factors. In this regard, compelling evidence demonstrates that depression can be the consequence of altered, and often maladaptive, response to adversities during pre- and early post-natal life. In this study, we investigated the impact of chronic maternal separation (MS) on the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) in serotonin transporter (SERT) knockout rats in the ventral and dorsal hippocampus as well as the ventromedial and dorsomedial prefrontal cortex (PFC). We found that both SERT deletion and the MS led to an overall reduction in Bdnf expression in the ventral hippocampus and the ventromedial PFC, whereas in the dorsal hippocampus and in the dorsomedial PFC, we observed a significant increase in the neurotrophin gene expression after MS exposure, specifically in the heterozygous SERT rats. In summary, we show that the modulation of Bdnf expression in SERT mutant rats exposed to MS reflects the complex functional consequences of this gene-environment interaction with a clear distinction between the ventral and the dorsal subfields of the hippocampus and of the PFC. Early life stress differently affects the expression of Bdnf in an anatomically distinct manner as a function of SERT genotype. Specifically, both SERT deletion and the maternal separation (MS) led to an overall reduction in Bdnf expression in the ventral hippocampus and in the ventromedial prefrontal cortex, whereas in the dorsal hippocampus and in the dorsomedial prefrontal cortex, we observed a significant increase in the neurotrophin gene expression after MS exposure specifically in the heterozygous SERT rats. We think that these findings may provide novel cues for modulating neurotrophin function, which is dys-regulated in several psychiatric conditions.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Calabrese
authors.forename: Rick H A
authors.initials: RH
authors.lastname: van der Doelen
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Guidotti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Tamas
authors.initials: T
authors.lastname: Kozicz
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
mesh_terms: D000818:Animals; D001010:Anxiety, Separation / Q000235:genetics / Q000523:psychology; D001923:Brain Chemistry / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000523:psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: maternal separation; neurotrophin; serotonin; ventral and dorsal hippocampus/prefrontal cortex