Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability

Citation
E. Costa et al., Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability, NEUROBIOL D, 8(5), 2001, pp. 723-742
Citations number
116
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROBIOLOGY OF DISEASE
ISSN journal
09699961 → ACNP
Volume
8
Issue
5
Year of publication
2001
Pages
723 - 742
Database
ISI
SICI code
0969-9961(200110)8:5<723:DSHADO>2.0.ZU;2-E
Abstract
In this review, we will first present a brief overview of the current under standing of: (a) the biology of reelin; (b) the putative reelin signaling p athways via integrin receptor stimulation; (c) the cytosolic adapter protei n DAB1, which appears to be operative in the transduction of reelin's pleio tropic actions in embryonic, adolescent, and adult brain; (d) the regulatio n of GABAergic function, including some aspects of GABAergic system develop ment; and (e) dendritic spine function and its role in the regulation of sy naptic plasticity. We argue that a downregulation of reelin expression occu rring in prefrontal cortex and in every brain structure of schizophrenia pa tients so far studied may be associated with a decrease in dendritic spine expression that in turn may provide an important reduction of cortical func tion as documented by the downregulation of glutamic acid decarboxylases, ( GAD(67)) expression, which might be secondary to a reduction:of GABAergic a xon terminals. This hypothesis is supported by a genetic mouse model of ree lin haploinsufficiency that replicates the above-described dendritic and pr esynaptic GABAergic defects documented in schizophrenia brains. (C) 2001 Ac ademic Press.