PMID:21814183

Citation	Teixeira, CM, Martín, ED, Sahún, I, Masachs, N, Pujadas, L, Corvelo, A, Bosch, C, Rossi, D, Martinez, A, Maldonado, R, Dierssen, M and Soriano, E (2011) Overexpression of Reelin prevents the manifestation of behavioral phenotypes related to schizophrenia and bipolar disorder. Neuropsychopharmacology 36:2395-405
Abstract	Despite the impact of schizophrenia and mood disorders, which in extreme cases can lead to death, recent decades have brought little progress in the development of new treatments. Recent studies have shown that Reelin, an extracellular protein that is critical for neuronal development, is reduced in schizophrenia and bipolar disorder patients. However, data on a causal or protective role of Reelin in psychiatric diseases is scarce. In order to study the direct influence of Reelin's levels on behavior, we subjected two mouse lines, in which Reelin levels are either reduced (Reelin heterozygous mice) or increased (Reelin overexpressing mice), to a battery of behavioral tests: open-field, black-white box, novelty-suppressed-feeding, forced-swim-test, chronic corticosterone treatment followed by forced-swim-test, cocaine sensitization and pre-pulse inhibition (PPI) deficits induced by N-methyl-D-aspartate (NMDA) antagonists. These tests were designed to model some aspects of psychiatric disorders such as schizophrenia, mood, and anxiety disorders. We found no differences between Reeler heterozygous mice and their wild-type littermates. However, Reelin overexpression in the mouse forebrain reduced the time spent floating in the forced-swim-test in mice subjected to chronic corticosterone treatment, reduced behavioral sensitization to cocaine, and reduced PPI deficits induced by a NMDA antagonist. In addition, we demonstrate that while stress increased NMDA NR2B-mediated synaptic transmission, known to be implicated in depression, Reelin overexpression significantly reduced it. Together, these results point to the Reelin signaling pathway as a relevant drug target for the treatment of a range of psychiatric disorders.
Links	PubMed PMC3194085 Online version:10.1038/npp.2011.153
Keywords	Animals; Bipolar Disorder/genetics; Bipolar Disorder/metabolism; Bipolar Disorder/prevention & control; Cell Adhesion Molecules, Neuronal/biosynthesis; Cell Adhesion Molecules, Neuronal/genetics; Cocaine/administration & dosage; Corticosterone/pharmacology; Exploratory Behavior/drug effects; Exploratory Behavior/physiology; Extracellular Matrix Proteins/biosynthesis; Extracellular Matrix Proteins/genetics; Female; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Mice, Transgenic; Nerve Tissue Proteins/biosynthesis; Nerve Tissue Proteins/genetics; Phenotype; Schizophrenia/genetics; Schizophrenia/metabolism; Schizophrenia/prevention & control; Sensory Gating/drug effects; Sensory Gating/physiology; Serine Endopeptidases/biosynthesis; Serine Endopeptidases/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:RELN	involved_in	GO:2000310: regulation of NMDA receptor activity	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:RELN	involved_in	GO:2000463: positive regulation of excitatory postsynaptic potential	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:RELN	involved_in	GO:0051968: positive regulation of synaptic transmission, glutamatergic	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:RELN		GO:0051968: positive regulation of synaptic transmission, glutamatergic	ECO:0000315:		P		Glutamatergic transmission was measured by electrophysiological recordings mice hippocampal neurons. NMDA mediated transmission was measured. There was increase in frequency EPSP response in reelin overexpression mice (figure 5a)	complete CACAO 2379
MOUSE:RELN		GO:2000463: positive regulation of excitatory postsynaptic membrane potential	ECO:0000315:		P		Glutamatergic transmission was measured by electrophysiological recordings mice hippocampal neurons. NMDA mediated transmission was measured. There was increase in frequency EPSP response in reelin overexpression mice (figure 5A).	complete CACAO 2380
MOUSE:RELN		GO:2000310: regulation of N-methyl-D-aspartate selective glutamate receptor activity	ECO:0000315:		P		Three stimulus trains were used to evoke to examine synaptic activation of NMDA receptors. Wild type showed reduced NMDA receptor mediated fEPSP compared to reelin overexpression mice figure 5B.	complete CACAO 2381

References

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