How immune cells in the brain can guide the treatment of neurodegenerative diseases

Human behavior depends on the excitement and inhibition of neurons, and scientists have long believed that neurons themselves play a major role in balancing this circuit of activity. But now, a research team led by Mount Sinai School of Medicine has discovered that immune cells in the brain also play an important role in behavioral regulation.

These immune cells, called microglia, are scavengers that get rid of dying cells.In a new study published in Nature, The team showed that, like inhibitory neurons, microglia can sense and suppress excessive neuronal activation. Researchers argued that the findings could affect the treatment of behavioral problems associated with neurodegenerative diseases.

“When we think about brain function, we usually think about how neurons control our thoughts and behaviors,” said Anne Schaefer, lead author of the study. Description In the statement. “But the brain also contains a large amount of non-neuronal cells, including microglia. Our study puts a new spotlight on these cells as a neuronal partner in the regulation of neural activity and behavior. . “

Schaefer et al. Reduced the number of mouse microglia by using a drug to inhibit the protein receptor CSF1R. By doing so, the animal became hypersensitive to neurostimulators. When they fed altered mice with neurostimulators, 90% of animals developed long-term epileptic seizures, indicating that neurons were overexcited. Only 11% of control animals experienced seizures.

Researchers have also identified the processes behind communication between neurons and microglia. When neurons are active, they release ATP, which provides energy for many of the activities of living cells. Microglia can detect and respond to ATP released from synaptic junctions between neurons.

How does this microglial-neuron interaction affect excitement and inhibition? Researchers have found that microglia break down ATP into adenosine (ADO), which acts on specific receptors on the surface of active neurons and suppresses their activation. The team reported that blocking the enzymes CD39 or CD73, which are involved in the conversion of ATP to ADO, reduced ADO levels and made mice more susceptible to seizures as a result of neurostimulators.

“This suggested to us that disease-related behavioral changes could be partially mediated by changes in microglial and neuronal communication,” Schaefer said.

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The role of microglial waste consumption has already become a popular target for researchers studying neurodegenerative diseases.A startup recently called Tranquis Therapeutics Revived We have spent $ 30 million to develop new drugs for neurodegenerative diseases that target microglial dysfunction based on its role in nerve cell inflammation. The company already has some animal data on amyotrophic lateral sclerosis, Parkinson’s disease, frontotemporal dementia, and age-related neuropathology.

Stanford University Team Exactly identified CD22, a B-cell receptor that contributes to the age-related decline in the ability of microglia to purify toxic debris of the central nervous system. Lowering the level of CD22 seemed to improve cognitive function in aged mice.

A team led by Mount Sinai is developing new treatments for behavioral disorders associated with neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease, where the discovery of interactions between neurons and microglia causes microglia to lose the ability to sense ATP. I think it has the potential to lead.

“The future promise of our research is also in the identification of new signals such as ATP that allow microglia to regulate the function of a wide variety of neurons, including those that control sleep and metabolism.” Schaefer added.