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The Journal of Neuroscience, December 15, 2000, 20(24):9086-9095

Agrin Controls Synaptic Differentiation in Hippocampal Neurons

Christian M. Böse¹, Dike Qiu¹, Andrea Bergamaschi³, Biagio Gravante³, Mario Bossi², Antonello Villa², Fabio Rupp¹, and Antonio Malgaroli³

¹ Department of Neuroscience, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, ² Microscopy and Image Analysis, University of Milan School of Medicine, and ³ Department of Biological and Technological Research, Scientific Institute San Raffaele, 20123 Milano, Italy

Agrin controls the formation of the neuromuscular junction. Whether it regulates the differentiation of other types of synapses remains unclear. Therefore, we have studied the role of agrin in cultured hippocampal neurons. Synaptogenesis was severely compromised when agrin expression or function was suppressed by antisense oligonucleotides and specific antibodies. The effects of antisense oligonucleotides were found to be highly specific because they were reversed by adding recombinant agrin and could not be detected in cultures from agrin-deficient animals. Interestingly, the few synapses formed in reduced agrin conditions displayed diminished vesicular turnover, despite a normal appearance at the EM level. Thus, our results demonstrate the necessity of agrin for synaptogenesis in hippocampal neurons.

Key words: agrin; synaptogenesis; synapses; primary hippocampal neurons; agrin antibodies; antisense oligonucleotides

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20249086-10$05.00/0

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