Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.577912/full |
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| author | Rashmi Gamage Ingrid Wagnon Ilaria Rossetti Ryan Childs Garry Niedermayer Rose Chesworth Erika Gyengesi |
| author_facet | Rashmi Gamage Ingrid Wagnon Ilaria Rossetti Ryan Childs Garry Niedermayer Rose Chesworth Erika Gyengesi |
| author_sort | Rashmi Gamage |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T19:16:24Z |
| format | Article |
| id | doaj.art-3269330da139409097287d3ac50e8a24 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-11T19:16:24Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3269330da139409097287d3ac50e8a242022-12-22T00:53:38ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-10-011410.3389/fncel.2020.577912577912Cholinergic Modulation of Glial Function During Aging and Chronic NeuroinflammationRashmi Gamage0Ingrid Wagnon1Ilaria Rossetti2Ryan Childs3Garry Niedermayer4Rose Chesworth5Erika Gyengesi6Department of Pharmacology, School of Medicine, Western Sydney University, Penrith, NSW, AustraliaDepartment of Pharmacology, School of Medicine, Western Sydney University, Penrith, NSW, AustraliaDepartment of Pharmacology, School of Medicine, Western Sydney University, Penrith, NSW, AustraliaDepartment of Pharmacology, School of Medicine, Western Sydney University, Penrith, NSW, AustraliaSchool of Science, Western Sydney University, Penrith, NSW, AustraliaSchool of Medicine, Western Sydney University, Penrith, NSW, AustraliaDepartment of Pharmacology, School of Medicine, Western Sydney University, Penrith, NSW, AustraliaAging 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.https://www.frontiersin.org/article/10.3389/fncel.2020.577912/fullcholinergic systemmicrogliaastrocytesbasal forebrainneuroinflammationaging |
| spellingShingle | Rashmi Gamage Ingrid Wagnon Ilaria Rossetti Ryan Childs Garry Niedermayer Rose Chesworth Erika Gyengesi Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation Frontiers in Cellular Neuroscience cholinergic system microglia astrocytes basal forebrain neuroinflammation aging |
| title | Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation |
| title_full | Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation |
| title_fullStr | Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation |
| title_full_unstemmed | Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation |
| title_short | Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation |
| title_sort | cholinergic modulation of glial function during aging and chronic neuroinflammation |
| topic | cholinergic system microglia astrocytes basal forebrain neuroinflammation aging |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.577912/full |
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