title: Secreted forms of beta-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons.
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 synaptogenesis 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 beta-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 beta-amyloid precursor protein antibodies showed that immunoreactivity was concentrated in axons and, particularly, in their growth cones. Because beta-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 dendritic responses to glutamate.
authors.affiliation: Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230.
authors.forename: M P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; C049925:fura-2-am; D018698:Glutamic Acid; D002118:Calcium; D016257:Fura-2