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
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.