Galantamine protects against hydrochloric acid aspirationinduced acute respiratory distress syndrome in rabbits

Yang, Yi; Peng, Yan; Yang, Jin

doi:10.4314/tjpr.v17i4.15

Cited by 8 publications

(8 citation statements)

References 11 publications

(12 reference statements)

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“…CNI-1493 binds to muscarinic acetylcholine receptors (mAChRs) (10) and administration of compounds that mimic the action of acetylcholine on mAChRs in the brain also suppresses circulating TNF and other pro-inflammatory cytokines (10–12). In addition, galantamine, an acetylcholinesterase inhibitor, which increases acetylcholine levels suppresses peripheral pro-inflammatory cytokine levels acting through a brain mAChR-mediated mechanism (13–15). These cholinergic effects in the brain are linked with activation of the vagus nerve-based inflammatory reflex (11, 13, 14, 16, 17), a physiological immunoregulatory circuit (18, 19) with recently demonstrated utility in treating human inflammatory diseases (20, 21).…”

Section: Introductionmentioning

confidence: 99%

Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation

et al. 2019

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The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF (TNFα) levels in murine endotoxemia. This effect was recapitulated by peripheral administration of the compound. BQCA also improved survival in murine endotoxemia and these effects were abolished in M1 mAChR knockout (KO) mice. Selective optogenetic stimulation of basal forebrain cholinergic neurons innervating brain regions with abundant M1 mAChR localization reduced serum TNF in endotoxemic mice. These findings reveal that forebrain cholinergic neurons regulate innate immune responses and inflammation, suggesting the possibility that in diseases associated with cholinergic dysfunction, including Alzheimer's disease this anti-inflammatory regulation can be impaired. These results also suggest novel anti-inflammatory approaches based on targeting forebrain cholinergic signaling in sepsis and other disorders characterized by immune dysregulation.

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Section: Introductionmentioning

confidence: 99%

Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation

et al. 2019

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“…This finding indicated that central action of acetylcholine on muscarinic acetylcholine receptors in the brain may suppress circulating TNFalpha and other proinflammatory cytokines. Similarly, the centrally acting acetylcholinesterase inhibitor galantamine suppressed an acid aspiration-induced acute respiratory syndrome in rabbits [11]. Consistent with the suspected association of cholinergic system integrity with inflammatory response, higher baseline expression of complement C3 in blood and a larger longitudinal increase of soluble TREM2 (sTREM2) levels in the CSF were associated with higher rates of atrophy of basal forebrain volume in cognitively healthy people with an increased CSF tau to amyloid ratio [12].…”

Section: Introductionmentioning

confidence: 66%

Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer’s Disease Spectrum

Teipel

Dyrba

Ballarini

et al. 2022

JAD

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Background: Inflammation has been described as a key pathogenic event In Alzheimer’s disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. Objective: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. Methods: We studied 261 cases from the DELCODE cohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. Results: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in Aβ 42/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. Conclusion: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aβ 42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.

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“…Chronic galantamine treatment (once daily, for two weeks) increases vagus nerve activity, alleviates splenic and renal inflammation, and decreases hypertension in this model (Pham et al., 2018). Additionally, brain mAChR‐mediated action of galantamine linked to the activation of the efferent arm of the inflammatory reflex alleviates acid‐induced acute lung injury/acute respiratory distress in rabbits (Yang et al, 2018).…”

Section: Cholinergic Signaling In the Regulation Of Inflammation And Galantamine As An Anti‐inflammatory Agentmentioning

confidence: 99%

Treating disorders across the lifespan by modulating cholinergic signaling with galantamine

Metz

Pavlov

2021

Journal of Neurochemistry

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Advances in understanding the regulatory functions of the nervous system have revealed neural cholinergic signaling as a key regulator of cytokine responses and inflammation. Cholinergic drugs, including the centrally acting acetylcholinesterase inhibitor, galantamine, which are in clinical use for the treatment of Alzheimer's disease and other neurodegenerative and neuropsychiatric disorders, have been rediscovered as anti‐inflammatory agents. Here, we provide a timely update on this active research and clinical developments. We summarize the involvement of cholinergic mechanisms and inflammation in the pathobiology of Alzheimer's disease, Parkinson's disease, and schizophrenia, and the effectiveness of galantamine treatment. We also highlight recent findings demonstrating the effects of galantamine in preclinical and clinical settings of numerous conditions and diseases across the lifespan that are characterized by immunological, neurological, and metabolic dysfunction.

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Galantamine protects against hydrochloric acid aspirationinduced acute respiratory distress syndrome in rabbits

Cited by 8 publications

References 11 publications

Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation

Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation

Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer’s Disease Spectrum

Treating disorders across the lifespan by modulating cholinergic signaling with galantamine

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