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Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after
Ukpong B Eyo1, Jiyun Peng1, Przemyslaw Swiatkowski1
1Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854.
Abstract:
Microglia are highly dynamic immune cells of the CNS and their dynamism is proposed to be regulated by neuronal activities. However, the mechanisms underlying neuronal regulation of microglial dynamism have not been determined. Here, we found an increased number of microglial primary processes in the hippocampus during KA-induced seizure activity. Consistently, global glutamate induced robust microglial process extension toward neurons in both brain slices and in the intact brain in vivo. The mechanism of the glutamate-induced microglial process extension involves the activation of neuronal NMDA receptors, calcium influx, subsequent ATP release, and microglial response through P2Y12 receptors. Seizure-induced increases in microglial process numbers were also dependent on NMDA receptor activation. Finally, we found that P2Y12 KO mice exhibited reduced seizure-induced increases in microglial process numbers and worsened KA-induced seizure behaviors. Our results elucidate the molecular mechanisms underlying microglia-neuron communication that may be potentially neuroprotective in the epileptic brain.
Insights
Neuronal activity regulates microglia, the CNS immune cells. This study reveals glutamate signaling via NMDA and P2Y12 receptors drives microglial process extension, potentially protecting the epileptic brain.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the central nervous system's immune cells, exhibit dynamic behavior.
- Neuronal activity is proposed to regulate microglial dynamism, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms of neuronal regulation of microglial dynamism.
- To investigate the role of microglia-neuron communication in seizure activity.
Main Methods:
- In vivo and in vitro studies using brain slices and intact brains.
- Utilized kainic acid (KA) to induce seizure activity.
- Employed P2Y12 knockout (KO) mice to assess receptor function.
Main Results:
- Glutamate stimulation induced robust microglial process extension toward neurons.
- This process involves neuronal NMDA receptor activation, calcium influx, ATP release, and microglial P2Y12 receptor activation.
- Seizure-induced increases in microglial processes were NMDA receptor-dependent.
- P2Y12 KO mice showed diminished microglial process increases and exacerbated seizure behaviors.
Conclusions:
- This study elucidates a key molecular pathway for microglia-neuron communication.
- The identified mechanism, involving NMDA and P2Y12 receptors, plays a role in regulating microglial responses during seizures.
- This communication pathway may offer neuroprotection in the epileptic brain.
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