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Updated: Jun 16, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Glutamate induces neurotrophic factor production from microglia via protein kinase C pathway
Jianfeng Liang1, Hideyuki Takeuchi, Shijie Jin
1Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Abstract:
Microglia are intrinsic immune cells in the central nervous system and play key roles in the pathogenesis of various central nervous system disorders. Microglia have been shown to attack damaged neurons by secreting a variety of neurotoxic factors including inflammatory cytokines, reactive oxygen species and glutamate. On the other hand, they can produce neurotrophic factors (NTFs) which support neuronal survival and growth. However, the precise mechanism that regulates microglial NTF production is not fully understood, and the relation between glutamate and NTFs remains unclear. In the present study, we show that glutamate significantly induces microglial NTF production by the activation of N-methyl-d-aspartate (NMDA) receptors, group III metabotropic glutamate receptors, and glutamate transporters. Activation of NMDA receptors and group III metabotropic glutamate receptors induces intracellular Ca(2+) release from the endoplasmic reticulum. Further, stimulation of glutamate transporters leads to influx of extracellular Ca(2+) in a Na(+)-dependent manner. This intracellular Ca(2+) elevation activates the protein kinase C pathway which induces microglial NTF expression and production. These results suggest that microglia play a neuroprotective role during the excitotoxic state in neurodegenerative diseases.
Insights
Glutamate stimulates microglia to produce neurotrophic factors (NTFs) that support neuron survival. This occurs via specific receptor activation and calcium signaling, suggesting a protective role for microglia in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system (CNS).
- Microglia can be neurotoxic but also produce neurotrophic factors (NTFs) for neuronal support.
- Mechanisms regulating microglial NTF production and the role of glutamate are not fully understood.
Purpose of the Study:
- To investigate how glutamate influences microglial neurotrophic factor (NTF) production.
- To elucidate the signaling pathways involved in glutamate-mediated NTF release from microglia.
Main Methods:
- Utilized N-methyl-d-aspartate (NMDA) receptors, group III metabotropic glutamate receptors, and glutamate transporters.
- Investigated intracellular Ca(2+) release and influx pathways.
- Examined the activation of the protein kinase C (PKC) pathway.
Main Results:
- Glutamate significantly induced microglial NTF production.
- Activation of NMDA and group III mGluRs triggered intracellular Ca(2+) release.
- Glutamate transporter stimulation caused Na(+)-dependent extracellular Ca(2+) influx.
- Elevated intracellular Ca(2+) activated the PKC pathway, leading to NTF expression.
Conclusions:
- Glutamate signaling via specific receptors and transporters promotes microglial NTF production.
- Intracellular calcium elevation and PKC activation are critical mediators.
- Microglia may exert a neuroprotective role in excitotoxic conditions associated with neurodegenerative diseases.
