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 language | English (US) |
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Pages (from-to) | 439-450 |
Number of pages | 12 |
Journal | Journal of Neurobiology |
Volume | 25 |
Issue number | 4 |
State | Published - 1994 |
Externally published | Yes |
Keywords
- Alzheimer's Disease
- calcium
- excitatory amino acids
- growth cone
- immunocytochemistry
- synaptic plasticity
ASJC Scopus subject areas
- General Neuroscience