Overexpression of the full-length neurotrophin receptor trkB regulates the expression of plasticity-related genes in mouse brain.
Significant body of evidence indicates an important role for brain-derived neurotrophic factor (BDNF) in the hippocampal synaptic plasticity; however, the exact mechanisms how the BDNF signal is converted to plastic changes during memory processes are under an intense investigation. To specifically address the role of the trkB receptor, we have previously generated transgenic mice overexpressing the full-length trkB receptor and observed a continuous activation of the trkB.TK+ receptor, improved learning and memory but an attenuated LTP in these mice. In this study, we describe the trkB.TK+ mRNA and protein distribution in the transgenic mice, showing the most prominent increase in the full-length trkB expression in the cortical layer V pyramidal neurons and dentate gyrus of the hippocampus. In addition, we have analyzed the mRNA expression patterns of a group of genes associated with both plastic changes in the nervous system and BDNF signaling. Regulated expression of immediate early genes c-fos, fra-2 and junB was observed in the transgenic mice. Furthermore, the mRNA expression of alpha-Ca2+/calmodulin-dependent kinase II (alpha-CaMKII) was reduced in both the hippocampus and parietal cortex, whereas growth-associated protein 43 (GAP-43) mRNA expressions were induced in the corresponding regions. Conversely, the mRNA expression of the transcription factor cAMP response element binding protein (CREB) was not altered in the trkB.TK+mice. Finally, the density of neuropeptide Y (NPY)-expressing cells was increased in the trkB.TK+ mice dentate hilus. Altogether, these results demonstrate in vivo that the increased trkB.TK+ signaling regulates several important plasticity-related genes.
Koponen
Eija
E
Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. BOX 1627, 70211 Kuopio, Finland. Eija.Koponen@uku.fi
Lakso
Merja
M
Castrén
Eero
E
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics*; D009478:Neuropeptide Y / Q000378:metabolism; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D009478:Neuropeptide Y; D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D012333:RNA, Messenger; D020813:Receptor, trkB; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517671:Camk2a protein, mouse