抄録
Neuregulin-1 (NRG1) and epidermal growth factor (EGF) bind to the ErbB receptor family and are suggested to be a risk gene for schizophrenia, although etiological or pathological mechanisms remain to be characterized. We reported that neonatal exposure to the proinflammatory cytokine, EGF, perturbs GABAergic development, leading to the behavioral and cognitive impairments that are often implicated in schizophrenia animal models. In the present study, we examined influences of in vivo NRG1 administration on GABAergic development and neurobehavioral consequences, and compared their behavioral characteristics with those induced by EGF. We produced and purified mouse Ig-NRG1beta protein (MW 25000) using the bacterial recombinant system and subcutaneously administered it to neonatal mice (C57BL/6J). Repeatedly injected Ig-NRG1beta permeated the blood-brain barrier and activated ErbB4 receptors in neonatal brain, promoting synaptic maturation of GABAergic neurons in the neocortex. At the adult stage, the Ig-NRG1beta-treated mice showed normal response in the fear-conditioning task, but were impaired in its latent learning paradigm. Prepulse inhibition (PPI) of the Ig-NRG1beta-treated mice was decreased, which are similar to the behavioral features of EGF-treated mice. These results suggest that endogenous production or release of NRG1 following brain injury and stress results in distinct cognitive and behavioral abnormalities. The therapeutic potential of ErbB receptor inhibitors will be discussed in these models. [J Physiol Sci. 2008;58 Suppl:S35]
