Cellular responses and functions of α7 nicotinic acetylcholine receptor activation in the brain: a narrative review

Abstract

The α7 nicotinic acetylcholine receptor (α7nAChR) has been studied for many years since its discovery. Although many functions and characteristics of brain α7nAChR are widely understood, much remains to be elucidated. The α7nAChR is widely expressed in the central nervous system, not only in neurons but also in astrocytes, microglia, and endothelial cells. α7nAChR can be activated by endogenous agonist like acetylcholine or exogenous agonists like nicotine and PNU282987. Its agonists can be divided into selective agonists and non-selective agonists. The activation of α7nAChR results in a series of physiological processes which have both short-term and long-term effects on cells, for example, calcium influx, neurotransmitter release, synaptic plasticity, and excitatory transmission. It also induces other downstream events, such as inflammation, autophagy, necrosis, transcription, and apoptosis. The cellular responses to α7nAChR activation vary according to cell types and conditions. For example, α7nAChR activation in pyramidal neurons leads to long-term potentiation, while α7nAChR activation in GABAergic interneurons leads to long-term depression. Studies have also shown some contradictory phenomena, which requires further study for clarification. Herein, the cellular responses of α7nAChR activation are summarized, and the functions of α7nAChR in neurons and non-neuronal cells are discussed. We also summarized contradictory conclusions to show where we stand and where to go for future studies.

Keywords: calcium influx; central nervous system diseases (CNS diseases); signaling pathway; synaptic plasticity; α7 nicotinic acetylcholine receptor (α7nAChR).

Figure 1

Cellular responses to α7nAChR activation. The activation of α7nAChR can lead to calcium influx directly, which can trigger neurotransmitter release, action potentials, synaptic plasticity, and calcium-induced calcium release. It can also activate the JAK2-STAT3 signaling pathway and further induce anti-apoptotic and anti-inflammatory effects. In addition, it also activates the AMPK-mTOR signaling pathway and induces autophagy. α7nAChR, α7 nicotinic acetylcholine receptor.