Expression of cholecystokinin, enkephalin, galanin and neuropeptide Y is markedly changed in the brain of the megencephaly mouse

Megencephaly, enlarged brain, is a major sign in several human neurological diseases. The mouse model for megencephaly (mceph/mceph) has an enlarged b rain, presumably due to brain cell hypertrophy, and exhibits neurological a nd motor disturbances with seizure-like activity, as well as disturbances i n the insulin-like growth factor system. Here, we report that expression of the neuropeptides cholecystokinin, enkephalin,,galanin and neuropeptide Y is dramatically changed in mceph/ mceph brains compared to wild type, as re vealed by in sih hybridization and immunohistochemistry. The changes were c onfined to discrete brain regions and occurred in a parallel fashion for pe ptides and their transcripts. For cholecystokinin, mceph/mceph brains had r egion-specific up- and down-regulations in several layers of the hippocampa l formation and increased levels in, especially ventral, cortical regions. Enkephalin messenger RNA expression was up-regulated in the dentate gyrus g ranular layer and in ventral cortices, but down-regulated in the CA1 pyrami dal layer. Enkephalin-like immunoreactivity was elevated in mossy fibers of the hippocampus and the ventral cortices. Galanin expression was increased in several layers and interneurons of the hippocampal formation, as well a s in ventral cortices. Galanin-like immunoreactivity was reduced in nerve t erminals in the forebrain. Neuropeptide Y expression was increased in the h ippocampal formation and ventral cortices. Whether the mainly increased peptide levels contribute to the excessive gro wth of the brain or represent a consequence of this growth and/or of the ne urological and motor disturbances remains to be elucidated. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.