title: Early and adult hippocampal TGF-β1 overexpression have opposite effects on behavior.
abstract: TGF-β1 is an anti-inflammatory cytokine that is augmented in the brain of autistic patients and that can affect brain development. In this work, we studied the effects of overexpressing TGF-β1 in the dentate gyrus of adult or young mice on behavior. TGF-β1 overexpression during postnatal development led to a long-term decrease in social interaction and to long-term increases in self-grooming and depression-related behaviors. Our analysis shows that these behavioral changes correlate with the long-term downregulation of TGF-β1 and IL-6 expression in the dentate gyrus, as well as to decreases in the mRNA levels of the synaptic protein neuroligin 3 and in the number of Reelin-positive neurons in the dentate gyrus. In contrast, chronic expression of TGF-β1 during adulthood led to transient opposite effects on these behaviors. These results show a central role of hippocampal TGF-β1 in the programming and modulation of social interaction, repetitive behavior and depression-related behavior. Finally, our data suggest a role of hippocampal TGF-β1 and early-life neuroinflammation in the development of the behavioral alterations observed in autism spectrum disorders.
authors.affiliation: Institute for Physiology, Molecular Biology and Neurosciences, CONICET-UBA, C1428EHA Buenos Aires, Argentina. adepino@conicet.gov.ar
authors.forename: Amaicha Mara
authors.initials: AM
authors.lastname: Depino
authors.forename: Luciana
authors.initials: L
authors.lastname: Lucchina
authors.forename: Fernando
authors.initials: F
authors.lastname: Pitossi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003863:Depression / Q000523:psychology; D005260:Female; D005911:Gliosis / Q000235:genetics; D006120:Grooming; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000091042:Reelin Protein; D013238:Stereotaxic Techniques; D013550:Swimming / Q000523:psychology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D000091042:Reelin Protein; D053773:Transforming Growth Factor beta1; C000717128:Reln protein, mouse