Secreted forms of β-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons

M. P. Mattson

Research output: Contribution to journalArticlepeer-review

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 β-amyloid precursor protein (APP(s)s) 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 APP(s)695 or APP(s)751. 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 APP(s)s can be released from axon terminals/growth cones in response to electrical activity, the present findings suggest that APP(s)s may play a role in developmental and synaptic plasticity by modulating dendritic responses to glutamate.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalJournal of Neurobiology
Volume25
Issue number4
StatePublished - 1994
Externally publishedYes

Keywords

  • Alzheimer's Disease
  • calcium
  • excitatory amino acids
  • growth cone
  • immunocytochemistry
  • synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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