Reelin down-regulation in mice and psychosis endophenotypes.

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Tueting P, Doueiri MS, Guidotti A, Davis JM, Costa E

Reelin down-regulation in mice and psychosis endophenotypes.

Neurosci Biobehav Rev. 2006;30(8):1065-77.

PubMed ID

16769115 [ View in PubMed

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Abstract

Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and in synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal but has been of interest as an animal model for psychosis since the discovery that reelin is 50% down-regulated in postmortem psychotic brain. Brain abnormalities in +/rl are similar to psychotic brain and include a reduction in glutamic acid de carboxylase 67 (GAD67), dendritic arbors and spine density in cortex and hippocampus, and abnormalities in synaptic function including long-term potentiation (LTP). In spite of these abnormalities, behavioral abnormalities in +/rl are subtle and controversial. Recent findings indicate that the reelin (RELN) and GAD67 promoters are hypermethylated in GABAergic neurons of psychotic postmortem brain and that DNA methyltransferase 1 (DNMT1) is up-regulated. Hypermethlyation of RELN and GAD67 promoters can be induced by treating mice with methionine, and these mice display brain and behavioral abnormalities similar to +/rl. Thus, an animal model that combines genetic heterozygocity with epigenesis holds promise for understanding the role of Reelin down-regulation in psychosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	Glutamate decarboxylase 1	Protein	Humans	Unknown	Not Available	Details