Title:Neurotransmitters and Microglial-Mediated Neuroinflammation
Volume: 14
Issue: 1
Author(s): Moonhee Lee
Affiliation:
Keywords:
Acetylcholine, adrenaline, ATP, GABA, glutamate, microglia
Abstract: Reciprocal interactions between cells caused by release of soluble factors are essential for brain function. So
far, little attention has been paid to interactions between neurons and glia. However, in the last few decades, studies regarding
such interactions have given us some important clues about possible mechanisms underlying degenerative processes
in neurological diseases such as Alzheimer’s disease and Parkinson’s disease. Activated microglia and markers of
inflammatory reactions have been consistently found in the post-mortem brains of diseased patients. But it has not been
clearly understood how microglia respond to neurotransmitters released from neurons during disease progression.
The main purpose of this review is to summarize studies performed on neurotransmitter receptor expression in microglia,
and the effects of their activation on microglial-mediated neuroinflammation. A possible mechanism underlying transmitter-
mediated modulation of microglial response is also suggested. Microglia express receptors for neurotransmitters such
as ATP, adenosine, glutamate, GABA, acetylcholine, dopamine and adrenaline. Activation of GABA, cholinergic and
adrenergic receptors suppresses microglial responses, whereas activation of ATP or adenosine receptors activates them.
This latter effect may be due primarily to activation of a Ca2+-signaling pathway which, in turn, results in activation of
MAP kinases and NFkB proteins with the release of proinflammatory factors. However, glutamate and dopamine are both
pro- and anti-inflammatory depending on the receptor subtypes expressed in microglia.
More detailed studies on downstream receptor-signaling cascades are needed to understand the roles of neurotransmitters
in controlling neuron-microglia interactions during inflammatory processes in disease progression. Such knowledge may
suggest new methods of treatment.