title: Lack of serotonin transporter alters BDNF expression in the rat brain during early postnatal development.
abstract: It is well established that alterations of the serotoninergic system may contribute to the pathophysiology of mood disorders. Accordingly, it has been demonstrated that genetic deletion of the serotonin transporter (SERT) in rodents leads to an anxious and depressive phenotype, which is also associated with reduced neuronal plasticity. Indeed, we have demonstrated that adult SERT(-/-) animals show decreased brain-derived neurotrophic factor (BDNF) expression, as well as reduced levels of transcription factor regulating the neurotrophin transcription. While these changes may represent long-term consequences of impaired function of the transporter during development, no information exists with respect to the developmental profile of such changes. Using SERT(-/-) rats at different ages, we found that the impairment in neuroplasticity originates early in development and worsens during the first 3 weeks of life. Indeed, we observed that BDNF expression was reduced at birth and that the magnitude of these changes became more pronounced starting from PND21, being sustained by epigenetic mechanisms as well as alterations in the expression of specific transcription factors, including Npas4 and CaRF. These results suggest that an impairment of SERT may affect BDNF expression throughout postnatal development. These early changes may increase stress susceptibility during critical windows of brain maturation, which may eventually lead to the heightened predisposition to mood disorders found in individual carrying genetic variants of the serotonin transporter.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita' degli Studi di Milano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Calabrese
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Guidotti
authors.forename: Anthonieke
authors.initials: A
authors.lastname: Middelman
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Judith
authors.initials: J
authors.lastname: Homberg
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000254:growth & development / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D020033:Protein Isoforms; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C508094:Gadd45b protein, rat; D000097642:GADD45 Proteins; C516513:Npas4 protein, rat; C493232:Slc6a4 protein, rat; C527692:calcium response transcription factor 1, rat
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