Dendritic Spine Hypoplasticity and Downregulation of Reelin and GABAergic Tone in Schizophrenia Vulnerability

Authors: Costa E.; Davis J.; Grayson D.R.; Guidotti A.; Pappas G.D.; Pesold C.

Source: Neurobiology of Disease, Volume 8, Number 5, October 2001 , pp. 723-742(20)

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Abstract:

In this review, we will first present a brief overview of the current understanding of: (a) the biology of reelin; (b) the putative reelin signaling pathways via integrin receptor stimulation; (c) the cytosolic adapter protein DAB1, which appears to be operative in the transduction of reelin's pleiotropic actions in embryonic, adolescent, and adult brain; (d) the regulation of GABAergic function, including some aspects of GABAergic system development; and (e) dendritic spine function and its role in the regulation of synaptic plasticity. We argue that a downregulation of reelin expression occurring in prefrontal cortex and in every brain structure of schizophrenia patients so far studied may be associated with a decrease in dendritic spine expression that in turn may provide an important reduction of cortical function as documented by the downregulation of glutamic acid decarboxylase₆₇ (GAD₆₇) expression, which might be secondary to a reduction of GABAergic axon terminals. This hypothesis is supported by a genetic mouse model of reelin haploinsufficiency that replicates the above-described dendritic and presynaptic GABAergic defects documented in schizophrenia brains. Copyright 2001 Academic Press.

Keywords: reelin; schizophrenia; bipolar disorder; psychosis; dendritic spines; GAD₆₇; reeler heterozygote; integrin

Language: English

Document Type: Review article

Affiliations: Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, 60612

Publication date: 2001-10-01