Reelin regulates postnatal neurogenesis and enhances spine hypertrophy and long-term potentiation.
Reelin, an extracellular protein essential for neural migration and lamination, is also expressed in the adult brain. To unravel the function of this protein in the adult forebrain, we generated transgenic mice that overexpress Reelin under the control of the CaMKIIalpha promoter. Overexpression of Reelin increased adult neurogenesis and impaired the migration and positioning of adult-generated neurons. In the hippocampus, the overexpression of Reelin resulted in an increase in synaptic contacts and hypertrophy of dendritic spines. Induction of long-term potentiation (LTP) in alert-behaving mice showed that Reelin overexpression evokes a dramatic increase in LTP responses. Hippocampal field EPSP during a classical conditioning paradigm was also increased in these mice. Our results indicate that Reelin levels in the adult brain regulate neurogenesis and migration, as well as the structural and functional properties of synapses. These observations suggest that Reelin controls developmental processes that remain active in the adult brain.
Pujadas
Lluís
L
Developmental Neurobiology and Regeneration Laboratory, Institute for Research in Biomedicine, Barcelona, Department of Cell Biology, University of Barcelona, and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED-ISCIII), 08028 Barcelona, Spain. lluis.pujadas@irbbarcelona.org
Gruart
Agnès
A
Bosch
Carles
C
Delgado
Lídia
L
Teixeira
Cátia M
CM
Rossi
Daniela
D
de Lecea
Luis
L
Martínez
Albert
A
Delgado-García
José M
JM
Soriano
Eduardo
E
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D003214:Conditioning, Classical; D049229:Dendritic Spines / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D017774:Long-Term Potentiation; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases