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

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.