α7 Nicotinic acetylcholine receptor-mediated anti-inflammatory actions modulate brain functions

The interaction between the immune system and the central nervous system is largely unknown and under intense scrutiny by the biomedical community. Research results during the last decades have identified important two-way communication processes between these two systems, mediated by the cytokine network as well as by “classical” neurotransmitters. The dogma of a separate functioning of the two systems has been conclusively challenged with the discovery that not only neurotransmitters affect immune system function, but also inflammation affects neuronal cells through the same “cytokine network” that connects the different components of the immune system. The “classical” transmitter acetylcholine is an important modulator of both neuronal and immune function through both muscarinic and nicotinic receptors. Among the latter, a7 nicotinic acetylcholine receptors (nAChRs) possess the peculiar property of being expressed in immune cells as well as in neurons. While the modulation of neuronal activity by direct activation of a7 nAChRs is relatively well described, the hypothesis that a7 nAChRs may influence neuronal behavior indirectly, through inhibition of inflammation, is a relatively new concept. This review aims to summarize the evidence that activation of a7 nAChRs may influence brain function not only by direct action on certain neuronal pathways, but also by reducing inflammation (central and/or peripheral), decreasing the levels of circulating cytokines and consequently, their influence on neuronal activity.