Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrenergic systems

Reciprocal interactions between glia and neurons are essential for many critical functions in brain health and disease. Microglial cells, the brain resident macrophages, and astrocytes, the most prevalent type of cell in brain, are actively involved in the control of neuronal activities both in developing and adult organisms. At the same time, neurons influence glial functions, through direct cell-to-cell interactions as well as the release of soluble mediators. Among signals from neurons that may have an active role in controlling glial activation are two major neurotransmitters: acetylcholine and noradrenaline. Several studies indicate that microglia and astrocytes express adrenergic receptors, whose activation influences the release of pro-inflammatory mediators, controlling the extent of glial reactivity. Acetylcholine receptors are also expressed by glial cells. In particular, microglial cells express the nicotinic receptor alpha7 and its activation attenuates the pro-inflammatory response of microglial cultures, suggesting that acetylcholine may control brain inflammation, in analogy to what demonstrated in peripheral tissues. Deficiencies of noradrenergic and cholinergic systems are linked to important neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) and it has been suggested that in addition to impairing neuron-to-neuron transmission, noradrenergic and cholinergic hypofunction may contribute to dysregulation of the normal neuron-glia interaction, abnormal glial reaction and, eventually, neurodegeneration. A deeper knowledge of role of cholinergic and noradrenergic systems in controlling neuron-glia interactions may offer new venues for disease treatments.