The plasticity of the central nervous system (CNS) in response to neuronal activity was suggested as early as 1894 by Cajal. Many neurodegenerative and neurological diseases are characterized by a dysfunction of the neuro-immune system, therefore, manipulation of this system has strong therapeutic potential.
For example, in humans, a link between neuronal activity and the addition of new myelin sheaths in the adult CNS has been demonstrated by studies on healthy subjects performing motor and memory tasks.
Astrocytes can further promote pro-inflammatory responses, recruit immune cells through the blood-brain barrier and modulate the number of activated microglial cells.
Cytokines, which are extracellular signaling proteins in the immune system, provide communication between neurons, astrocytes and immune cells.
Previous work has shown that the exposure of mice to lights flashing at 40 Hz, leads to neuronal activity at gamma frequency (∼40 Hz) and the recruitment of microglia, which are the main immune cells of the brain.
However, the mechanisms of biochemical signaling between neuronal activity at 40 Hz and immune recruitment remain unknown. Here, the scientists exposed male wild-type mice at 5–60 min of 40 Hz, controlled the flicker and evaluated the networks of cytokines and phosphoproteins known to play a role in immune function. Exposing mice to LED bands flashing at 40 Hz, is known to induce gamma neural activity.
These scientists discovered that the 40 Hz flicker results in increased expression of cytokines that promote phagocytic microglial states, such as IL-6 and IL-4, and increased expression of microglial chemokines. Interestingly, the effects of cytokines differed depending on the frequency of stimulation, revealing a range of neuroimmune effects.
Scientists have discovered that 40 Hz flicker regulates NF-κB and MAPK.
The phospho-signaling in the NF-κB pathway was significantly upregulated after 15 min, but not 5 or 60 min, of 40 Hz compared to random flicker.
While the phosphorylation profiles of MAPK were similar to those of NF-κB, they had different kinetics. The MAPK phospho-signaling was significantly different between 40 Hz and the random groups after 60 min of flicker but not after 5 or 15 min.
These results are the first, to the researchers' knowledge, to show how visual stimulation rapidly induces critical neuroimmune signaling in healthy animals. Different forms of visual stimulation have induced unique cytokine profiles. Thus, flicker stimulation can be used to quickly and non-invasively manipulate the signaling and expression of genes regulating neuronal immune activity. It is important to note that all the researchers carried out their analyzes on wild type animals.
