Medical Research

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Kristen Sparrow • July 04, 2022

San Francisco Sity Sights. Nob Hill

This is key to understanding how vagal activity, or cholinergic activity can mitigate the chronic inflammation found with Alzheimer’s disease.  I have highlighted below the role of the (intimidating sounding) α7 nicotinic acetylcholine (α7nACh) receptors. These are receptors that are stimulated by acetylcholine the neurotransmitter found in vagal, or parasympathetic activity.  These receptors are targeted in research on direct implanted vagal nerve stimulators.  But they are also stimulated by acupuncture.

This is one more reason why the calming effects of acupuncture are important to overall health because of its anti-inflammatory effects.  It is also a reason that the focus of my research has been on vagal activity with acupuncture.

Gamage R, Wagnon I, Rossetti I, et al. Cholinergic Modulation of Glial Function During Aging and Chronic NeuroinflammationFront Cell Neurosci. 2020;14:577912. Published 2020 Oct 15. doi:10.3389/fncel.2020.577912

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Rashmi Gamage, Ingrid Wagnon, […], and Erika Gyengesi

Additional article information


Aging is a complex biological process that increases the risk of age-related cognitive degenerative diseases such as dementia, including Alzheimer’s disease (AD), Lewy Body Dementia (LBD), and mild cognitive impairment (MCI). Even non-pathological aging of the brain can involve chronic oxidative and inflammatory stress, which disrupts the communication and balance between the brain and the immune system. There has been an increasingly strong connection found between chronic neuroinflammation and impaired memory, especially in AD. While microglia and astrocytes, the resident immune cells of the central nervous system (CNS), exerting beneficial effects during the acute inflammatory phase, during chronic neuroinflammation they can become more detrimental. Central cholinergic circuits are involved in maintaining normal cognitive function and regulating signaling within the entire cerebral cortex. While neuronal-glial cholinergic signaling is anti-inflammatory and anti-oxidative, central cholinergic neuronal degeneration is implicated in impaired learning, memory sleep regulation, and attention. Although there is evidence of cholinergic involvement in memory, fewer studies have linked the cholinergic anti-inflammatory and anti-oxidant pathways to memory processes during development, normal aging, and disease states. This review will summarize the current knowledge of cholinergic effects on microglia and astroglia, and their role in both anti-inflammatory and anti-oxidant mechanisms, concerning normal aging and chronic neuroinflammation. We provided details on how stimulation of α7 nicotinic acetylcholine (α7nACh) receptors can be neuroprotective by increasing amyloid-β phagocytosis, decreasing inflammation and reducing oxidative stress by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) pathways and decreasing the release of pro-inflammatory cytokines. There is also evidence for astroglial α7nACh receptor stimulation mediating anti-inflammatory and antioxidant effects by inhibiting the nuclear factor-κB (NF-κB) pathway and activating the Nrf2 pathway respectively. We conclude that targeting cholinergic glial interactions between neurons and glial cells via α7nACh receptors could regulate neuroinflammation and oxidative stress, relevant to the treatment of several neurodegenerative diseases.

Keywords: cholinergic system, microglia, astrocytes, basal forebrain, neuroinflammation, aging, neurodegeneration