Nicotinic Acetylcholine Receptors in Regulation of Pathology of Cerebrovascular Disorders

Katsuki, Hiroshi; Matsumoto, Kosei

doi:10.1007/978-981-10-8488-1_7

Cited by 4 publications

(5 citation statements)

References 68 publications

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“…2015). Rodent studies and cell culture experiments show that binding of ACh to the α7nAChR on microglia leads to decreased production of proinflammatory cytokines (see also “Peripheral cholinergic links of brain disorders”) (Morioka et al 2018; Katsuki & Matsumoto, 2018). Additionally, it has been postulated that stimulation of this receptor may influence the expression of microglial glutamate transporters, in turn reducing harmful excitotoxicity after brain injury and leading to neuroprotective effects.…”

Section: Brain Disorders With Affected Cholinergic Signalingmentioning

confidence: 99%

Regulators of cholinergic signaling in disorders of the central nervous system

Winek

Soreq

Meisel

2021

Journal of Neurochemistry

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Cholinergic signaling is crucial in cognitive processes, and degenerating cholinergic projections are a pathological hallmark in dementia. Use of cholinesterase inhibitors is currently the main treatment option to alleviate symptoms of Alzheimer's disease and has been postulated as a therapeutic strategy in acute brain damage (stroke and traumatic brain injury). However, the benefits of this treatment are still not clear. Importantly, cholinergic receptors are expressed both by neurons and by astrocytes and microglia, and binding of acetylcholine to the α7 nicotinic receptor in glial cells results in anti‐inflammatory response. Similarly, the brain fine‐tunes the peripheral immune response over the cholinergic anti‐inflammatory axis. All of these processes are of importance for the outcome of acute and chronic neurological disease. Here, we summarize the main findings about the role of cholinergic signaling in brain disorders and provide insights into the complexity of molecular regulators of cholinergic responses, such as microRNAs and transfer RNA fragments, both of which may fine‐tune the orchestra of cholinergic mRNAs. The available data suggest that these small noncoding RNA regulators may include promising biomarkers for predicting disease course and assessing treatment responses and might also serve as drug targets to attenuate signaling cascades during overwhelming inflammation and to ameliorate regenerative capacities of neuroinflammation.

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Section: Brain Disorders With Affected Cholinergic Signalingmentioning

confidence: 99%

Regulators of cholinergic signaling in disorders of the central nervous system

Winek

Soreq

Meisel

2021

Journal of Neurochemistry

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“…Activation of α 7 -AChR has been shown to be a therapeutic target capable of preventing neuroinflammation, neuronal cell loss, blood-brain barrier disruption, and brain edema in numerous rodent models of brain injuries, including SAH [15], traumatic brain injury [14,23], and intracerebral hemorrhage [13,16,41,42]. In these studies, various agonists were used, but none have been translated into clinical practice.…”

Section: Implications For Human Usementioning

confidence: 99%

“…Furthermore, acetylcholine levels in cerebrospinal fluid after aSAH are significantly lower in the acute phase of illness, suggesting that reduced Ach receptor activity may play a role in SAH injury [12]. α 7 -AChR agonists have been reported to offer benefit after a number of hemorrhagic insults to the brain including intracerebral hemorrhage [13], traumatic brain injury [14], and SAH [15]. Specifically, agonism of α 7 -AChR has been observed to provide anti-inflammatory and anti-apoptotic mechanisms which can improve outcome from experimental hemorrhagic stroke.…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, agonism of α 7 -AChR has been observed to provide anti-inflammatory and anti-apoptotic mechanisms which can improve outcome from experimental hemorrhagic stroke. Studies have indicated that α 7 -AChR signaling can produce anti-inflammatory effects via JAK2 [13,16] or IRAK-M pathways [17]. JAK2 signaling negatively regulates inflammation via STAT phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

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α7-Acetylcholine Receptor Signaling Reduces Neuroinflammation After Subarachnoid Hemorrhage in Mice

et al. 2021

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Aneurysmal subarachnoid hemorrhage (aSAH) causes a robust inflammatory response which leads worse brain injury and poor outcomes. We investigated if stimulation of nicotinic acetylcholine α 7 receptors (α 7 -AChR) (receptors shown to have anti-inflammatory effects) would reduce inflammation and improve outcomes. To investigate the level of peripheral inflammation after aSAH, inflammatory markers were measured in plasma samples collected in a cohort of aSAH patients. To study the effect of α 7 -AChR stimulation, SAH was induced in adult mice which were then treated with a α 7 -AChR agonist, galantamine, or vehicle. A battery of motor and cognitive tests were performed 24 h after subarachnoid hemorrhage. Mice were euthanized and tissue collected for analysis of markers of inflammation or activation of α 7 -AChR-mediated transduction cascades. A separate cohort of mice was allowed to survive for 28 days to assess long-term neurological deficits and histological outcome. Microglia cell culture subjected to hemoglobin toxicity was used to assess the effects of α 7 -AChR agonism. Analysis of eighty-two patient plasma samples confirmed enhanced systemic inflammation after aSAH. α 7 -AChR agonism reduced neuroinflammation at 24 h after SAH in male and female mice, which was associated with improved outcomes. This coincided with JAK2/STAT3 and IRAK-M activity modulations and a robust improvement in neurological/cognitive status that was effectively reversed by interfering with various components of these signaling pathways. Pharmacologic inhibition partially reversed the α 7 -AChR agonist's benefits, supporting α 7 -AChR as a target of the agonist's therapeutic effect. The cell culture experiment showed that α 7 -AChR agonism is directly beneficial to microglia. Our results demonstrate that activation of α 7 -AChR represents an attractive target for treatment of SAH. Our findings suggest that α 7 -AChR agonists, and specifically galantamine, might provide therapeutic benefit to aSAH patients.

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“…This additional muscarinic activity of huprineX is significant and offers therapeutic advantages in dementia therapy. 28…”

Section: Cholinergic Receptorsmentioning

confidence: 99%

Huperzinea: Pharmacological and Therapeutic Potential

Dubey¹,

Ahmad²,

Sharma³

et al. 2020

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Introduction: Huperzine A (HupA) is derived from a club moss (Huperzia serrata). It is a potent and reversible inhibitor of acetyl cholinesterase (AChE). Chemically, it is a sesquiterpene alkaloid. It has been used for the treatment of swelling, fever and blood disorders for centuries in China. Methodology: The literature available on Huperzine was thoroughly studied. It has shown much beneficial effect since ages. It is a established Nootropic agent and widely used in the treatment of Alzheimer's disease. The plant has shown promising results in vivo and in vitro studies. Results and Conclusion: The present review highlights the pharmacological potential of Huperzine with its pharmacokinetic and pharmacokinetic studies and it's rational for future prospective.

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Nicotinic Acetylcholine Receptors in Regulation of Pathology of Cerebrovascular Disorders

Cited by 4 publications

References 68 publications

Regulators of cholinergic signaling in disorders of the central nervous system

Regulators of cholinergic signaling in disorders of the central nervous system

α7-Acetylcholine Receptor Signaling Reduces Neuroinflammation After Subarachnoid Hemorrhage in Mice

Huperzinea: Pharmacological and Therapeutic Potential

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