Acetylcholine suppresses microglial inflammatory response via αnAChR to protect hippocampal neurons

Lin, Li; Li, Zhan; Jiang, Yong-Ying; Shen, Weixing; Peng, Yu‐Ping; Qiu, Yihua

doi:10.31083/j.jin.2019.01.114

Cited by 20 publications

(14 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A higher concentration of ACh markedly inhibited the LPS-induced microglial inflammatory response by decreasing pro-inflammatory factors and inhibiting hippocampal neuronal apoptosis, showing that ACh has concentration-dependent anti-inflammatory and neuroprotection properties in this model (Li L. et al, 2019). They also demonstrated, by genetic knockdown of α7nAChR, that both the anti-inflammatory and neuroprotective abilities of ACh depend on microglial α7nAChR signaling (Li L. et al, 2019). In a model of oxaliplatininduced neurotoxicity in co-cultured neurons and astrocytes, the application of an α7nAChR agonist increased neuron viability by preventing caspase-3 activation, increased glutamine synthetase expression levels, and increased the production of the anti-inflammatory cytokine TGF-β (Di Cesare Mannelli et al, 2015).…”

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 64%

“…The exact mechanism by which activation of nAChR on astroglia or microglia can lead to an anti-inflammatory effect is still under investigation. A recent study applied ACh to rat hippocampal neuron-microglia co-cultures to confirm its anti-inflammatory properties in response to microglia-derived neuroinflammation (Li L. et al, 2019). A higher concentration of ACh markedly inhibited the LPS-induced microglial inflammatory response by decreasing pro-inflammatory factors and inhibiting hippocampal neuronal apoptosis, showing that ACh has concentration-dependent anti-inflammatory and neuroprotection properties in this model (Li L. et al, 2019).…”

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 97%

“…A recent study applied ACh to rat hippocampal neuron-microglia co-cultures to confirm its anti-inflammatory properties in response to microglia-derived neuroinflammation (Li L. et al, 2019). A higher concentration of ACh markedly inhibited the LPS-induced microglial inflammatory response by decreasing pro-inflammatory factors and inhibiting hippocampal neuronal apoptosis, showing that ACh has concentration-dependent anti-inflammatory and neuroprotection properties in this model (Li L. et al, 2019). They also demonstrated, by genetic knockdown of α7nAChR, that both the anti-inflammatory and neuroprotective abilities of ACh depend on microglial α7nAChR signaling (Li L. et al, 2019).…”

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 99%

See 2 more Smart Citations

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Gamage

Wagnon

Rossetti

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 64%

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 97%

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 99%

See 1 more Smart Citation

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Gamage

Wagnon

Rossetti

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The α7 nAChRs expressed in myeloid cells, including microglia, are involved in the cholinergic anti-inflammatory pathway. Upon activation, they attenuate the production of pro-inflammatory cytokines like IL-1β, IL-6, or TNFα [98,[102][103][104][105]. Downregulation of α7 nAChRs in activated microglia results in reduced pro-survival and anti-oxidant signaling [106][107][108].…”

Section: Enhancing the α7 Nachr Functionmentioning

confidence: 99%

Changing Functional Signatures of Microglia along the Axis of Brain Aging

Brawek

Skok

Garaschuk

2021

IJMS

View full text Add to dashboard Cite

Microglia, the innate immune cells of the brain, are commonly perceived as resident macrophages of the central nervous system (CNS). This definition, however, requires further specification, as under healthy homeostatic conditions, neither morphological nor functional properties of microglia mirror those of classical macrophages. Indeed, microglia adapt exceptionally well to their microenvironment, becoming a legitimate member of the cellular brain architecture. The ramified or surveillant microglia in the young adult brain are characterized by specific morphology (small cell body and long, thin motile processes) and physiology (a unique pattern of Ca2+ signaling, responsiveness to various neurotransmitters and hormones, in addition to classic “immune” stimuli). Their numerous physiological functions far exceed and complement their immune capabilities. As the brain ages, the respective changes in the microglial microenvironment impact the functional properties of microglia, triggering further rounds of adaptation. In this review, we discuss the recent data showing how functional properties of microglia adapt to age-related changes in brain parenchyma in a sex-specific manner, with a specific focus on early changes occurring at middle age as well as some strategies counteracting the aging of microglia.

show abstract

“…And, ACh reduced secretion of pro inflammatory factors and reduced the pro-apoptotic effects of activated microglia on neurons. These effects of ACh were abolished when α7nAChR was silenced using α7 nAChR-shRNA [47].…”

Section: Natural Killer Cellsmentioning

confidence: 99%

Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3

Mizrachi¹,

Vaknin‐Dembinsky²,

Brenner³

et al. 2021

Molecules

View full text Add to dashboard Cite

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in or on various cell types and have diverse functions. In immune cells nAChRs regulate proliferation, differentiation and cytokine release. Specifically, activation of the α7 nAChR reduces inflammation as part of the cholinergic anti-inflammatory pathway. Here we review numerous effects of α7 nAChR activation on immune cell function and differentiation. Further, we also describe evidence implicating this receptor and its chaperone RIC-3 in diseases of the central nervous system and in neuroinflammation, focusing on multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Deregulated neuroinflammation due to dysfunction of α7 nAChR provides one explanation for involvement of this receptor and of RIC-3 in neurodegenerative diseases. In this review, we also provide evidence implicating α7 nAChRs and RIC-3 in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) involving neuroinflammation. Besides, we will describe the therapeutic implications of activating the cholinergic anti-inflammatory pathway for diseases involving neuroinflammation.

show abstract

Acetylcholine suppresses microglial inflammatory response via αnAChR to protect hippocampal neurons

Abstract: J o u r n a l o f I n t e g r a t i v e N e u r o s c i e n c e

Cited by 20 publications

References 29 publications

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Changing Functional Signatures of Microglia along the Axis of Brain Aging

Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3

Contact Info

Product

Resources

About