A neuron-glia crosstalk under exposure to methamphetamine
Exposure to psychostimulants has been classically associated with damage to neuronal terminals. However, it is now accepted that addiction results from the interaction between neuronal and glial cells. We hypothesize that the long-term adverse consequences occurring within the brain’s reward circuitry under psychostimulant exposure may be due, at least in part, to the underlying neuroinflammatory process, and that limiting inflammation may be relevant to control the addictive behavior.
We have verified that Meth cannot stimulate microglia in a cell-autonomous manner, and therefore, we hypothesized that a crosstalk with other types of cells is likely necessary to activate microglia in such conditions. Here, we are interested in clarifying the crosstalk between neurons and microglia under Meth exposure.
To explore this issue we have evaluated the microglial activation profile in co-cultures of microglia and neurons performed in microfluidic devices. Our results seem to indicate that neurons under Meth-exposure may attempt to shift microglial cells to an anti-inflammatory profile, decreasing iNOS expression. We further exposed microglial cells co-cultured with neuronal cells to the conditioned medium obtained from astrocytes treated with Meth. We show that neurons still attempt to induce an anti-inflammatory profile in microglia, as evidenced by the increase of arginase and the decrease of Il1-ß expression.
To further dissect the modulation of microglia activation by neurons, neuroimmune regulatory molecules expressed by neurons and which target receptors are present in microglia cells were addressed in the hippocampus and striatum of mice submitted to a binge administration of Meth. The results show that several of these molecules are altered differently in these two regions (CD200-CD200r; CD47-CD172a and CD95), in which we have previously observed a neuroinflammatory process under Meth exposure. These neuroimmune regulatory molecules are presently being explored in neuron-microglia co-cultures in order to clarify the importance of such regulators in the neuroinflammatory process caused by Meth.
In summary, our results indicate that neurons play an important role in shifting microglia to a less inflammatory profile under Meth-exposure, which may be an important neuroprotective pathway.