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Carbachol increases intracellular free calcium in cultured rat microglia
E R Whittemore1, A R Korotzer, A Etebari
1Irvine Research Unit in Brain Aging, University of California 92717.
Abstract:
Microglia are resident macrophages in the CNS and have been shown to exhibit immune system responses common to other macrophages, including phagocytosis, secretion of superoxide anions, and secretion of regulatory and trophic factors such as interleukin-1. Phagocytosis and oxidative burst by macrophages are often reported to be preceded by an increase in cytosolic free calcium. In addition, a variety of compounds, including neuroactive peptides, have been shown to elicit such calcium responses in various macrophage preparations. The results presented demonstrate that cultured rat microglia respond to exposure to carbachol with an increase in intracellular free calcium which is atropine-sensitive and the result of the release of calcium from intracellular stores. Norepinephrine also induced increases in free calcium, whereas the metabotropic glutamate agonist 1S,3R-ACPD, serotonin, adenosine and ATP did not. These results suggest that microglia can respond to select neurotransmitters, and that there may exist a signaling loop between neurons and microglia. Furthermore, since cholinergic fibers have been shown to infiltrate neuritic plaques in Alzheimer's disease (AD) and microglia have been reported to be activated in plaques, these results suggest that interactions between select neurotransmitters and microglia may play a key role in neurodegenerative diseases.
Insights
Cultured microglia, the brain's immune cells, increase intracellular calcium in response to carbachol and norepinephrine. This suggests neurotransmitter signaling may influence neuroinflammation in diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS).
- Like peripheral macrophages, microglia perform immune functions such as phagocytosis and oxidative burst.
- These macrophage functions are often preceded by increased intracellular free calcium levels.
Purpose of the Study:
- To investigate the response of cultured rat microglia to neurotransmitters.
- To determine if microglia exhibit calcium signaling in response to specific neuroactive compounds.
- To explore potential neuronal-microglial communication pathways.
Main Methods:
- Cultured rat microglia were exposed to various neurotransmitters and agonists.
- Intracellular free calcium levels were measured.
- The effects of atropine were assessed to determine the source of calcium release.
Main Results:
- Carbachol induced an atropine-sensitive increase in intracellular free calcium in microglia.
- Norepinephrine also elevated intracellular free calcium levels.
- Metabotropic glutamate agonist (1S,3R-ACPD), serotonin, adenosine, and ATP did not elicit a significant calcium response.
Conclusions:
- Cultured microglia respond to specific neurotransmitters like carbachol and norepinephrine.
- These responses involve the release of calcium from intracellular stores.
- Neurotransmitter-microglia interactions may play a role in neurodegenerative diseases, such as Alzheimer's disease, due to activated microglia in plaques.