Abstract: | In addition to being the major excitatory neurotransmitter in the mammalian brain, glutamate is believed to play a key role in the regulation of neurite outgrowth and snaptogenesis during development. In cultured embryonic hippocampal pyramidal neurons, glutamate inhibits dendrite outgrowth by a mechanism involving elevation of intracellular-free calcium levels (Ca2+]i). In the present study, secreted forms of the β-amyloid precursor protein (APPss) counteracted the inhibitory effect of glutamate on dendrite outgrowth in cultured embryonic hippocampal neurons. The prolonged elevation of Ca2+]i normally induced by glutamate was significantly attenuated in neurons that had been pretreated with 2–10 nM of APPs695 or APPs751. Immunocytochemistry with β-amyloid precursor protein antibodies showed that immunoreactivity was concentrated in axons and, particularly, in their growth cones. Because β-amyloid precursor proteins are axonally transported, and APPss can be released from axon terminals/growth cones in response to electrical activity, the present findings suggest that APPss may play a role in developmental and synaptic plasticity by modulating dentritic responses to glutamate. 1994 John Wiley & Sons, Inc. |