Calcium channels affect neuroinflammation and motivation

As described above, microglia is the main group of immune cells in the brain. In a healthy state, they maintain a stable internal environment, but when injured or diseased, they transition to a reactive state that can contribute to inflammation.

A new study has shown that this transition is regulated by the Orai1 calcium channels. Scientists have discovered that these channels allow calcium ions to enter the cells, triggering the activation of genes responsible for immune response and cellular metabolism. In experiments on mice, it was observed that in the absence of these channels, microglia loses its ability to transition into an aggressive pro-inflammatory state. Instead, the cells begin to actively secrete antimicrobial and neuroprotective substances, including the protein BDNF, which is critical for the growth and survival of neurons.

Physiological changes in microglia have a direct impact on behavior and mental state. In particular, inflammatory processes in the hippocampus, triggered by the release of cytokines IL-1 beta and IL-6, lead to impaired motivation and reduced ability to seek rewards. The removal of Orai1 channels in the experimental animals prevented these negative changes, keeping their motivational indicators normal even under stress.

This discovery makes Orai1 channels a promising target for the development of new-generation drugs. Inhibiting these channels could be an effective method for treating depression, neurodegenerative diseases, and chronic pain. The uniqueness of this approach lies in the fact that blocking Orai1 not only suppresses inflammation, but also reprograms the brain’s immune cells to promote tissue repair and support the nervous system.