Secreted forms of beta-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons.
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.
Mattson
M P
MP
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230.
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
D016564:Amyloid beta-Protein Precursor; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; C049925:fura-2-am; D018698:Glutamic Acid; D002118:Calcium; D016257:Fura-2