Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Conejero-Goldberg, Concepción; Davies, Peter; Ulloa, Luis

doi:10.1016/j.neubiorev.2007.10.007

Cited by 83 publications

(62 citation statements)

References 149 publications

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“…[43][44][45][46] Therefore, we investigated the role of the ␣7nAChR in inflammation and EOD in renovascular hypertension using ␣7nAChR Ϫ/Ϫ mice. After induction of 2K1C hypertension, ␣7nAChR Ϫ/Ϫ mice displayed greater serum levels of proinflammatory cytokines (⌱L-1␤ , IL-6, and TNF-␣) and more severe EOD than WT mice.…”

Section: Et Al ␣7nachr and Hypertensive Organ Damage 303mentioning

confidence: 99%

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Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

et al. 2011

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Abstract-Inflammatory responses are associated with the genesis and progression of end-organ damage (EOD) in hypertension. A role for the ␣7 nicotinic acetylcholine receptor (␣7nAChR) in inflammation has recently been identified. We tested the hypothesis that ␣7nAChR dysfunction contributes to hypertensive EOD. In both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta coarctation-induced hypertension, atropine-induced tachycardia was blunted compared with normotensive controls. Both models of hypertension were associated with deficits in expression of the vesicular acetylcholine transporter and the ␣7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta coarctation, deficits in aortic vesicular acetylcholine transporter and ␣7nAChR were present both above and below the coarctation site, indicating that they were independent of the level of arterial pressure itself. Hypertension in 40-week-old SHRs was associated with cardiac and aortic hypertrophy. Morphological abnormalities consistent with EOD, along with elevated tissue levels of proinflammatory cytokines (tumor necrosis factor-␣, interleukin-1␤, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic treatment of SHRs with the ␣7nAChR agonist PNU-282987 relieved EOD and inhibited tissue levels of proinflammatory cytokines and activation of nuclear factor B. Greater serum levels of proinflammatory cytokines and more severe damage in the heart, aorta, and kidney were seen in ␣7nAChR Ϫ/Ϫ mice subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis of EOD in models of hypertension of varying etiology. This pathway may provide a new target for preventing cardiovascular disease resulting from hypertension. (Hypertension. 2011;57:298-307.) • Online Data Supplement Key Words: acetylcholine Ⅲ ␣7 nicotinic acetylcholine receptor Ⅲ inflammation Ⅲ hypertension Ⅲ end-organ damage H ypertension is a major risk factor for myocardial infarction, heart failure, stroke, and kidney dysfunction. Endorgan damage (EOD), including cardiac hypertrophy and myocyte dysfunction, vascular remodeling, and renal lesions, is a crucial mediatory link between hypertension and the development of these cardiovascular events. 1 Therefore, a better understanding of the mechanisms leading to hypertensive EOD could provide new avenues for prevention of cardiovascular events. Inflammation is very important in the genesis and development of EOD. 2,3 Furthermore, the reninangiotensin system can contribute to EOD, at least partly by promoting inflammation. 4 -7 However, cardiovascular inflammation and EOD can also occur without renin-angiotensin system activation, 8 so other mechanisms must also operate.Recent evidence indicates that neuronal 9 -11 cholinergic systems influence inflammatory responses by controlling the release of tumor necrosis factor (TNF)-␣, interleukin-(⌱L)-1␤, and IL-6 and that nonneuronal acetylcholine synthesis and rele...

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Section: Et Al ␣7nachr and Hypertensive Organ Damage 303mentioning

confidence: 99%

“…12 At the same time, the aorta was cleaned of adhering fat and connective tissue. A leupeptin (50 µg/ml), aprotinin (25 µg/ml), pesptatin A (10μg/ml) and dithiothreitol 43 (DTT2 mmol/L). The supernatant was obtained by centrifugation at 11,000 g for 15 min 44 at 4°C.…”

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Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

et al. 2011

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“…Recent work has shown that ACh released from cholinergic axon terminals can interact with α7 nicotinic ACh receptors (nAChRs) on vicinal immune cells [38,39] . The nicotinic receptors then translate the cholinergic signal into suppression of cytokine release [37,40] .…”

Section: Cholinergic Deficiency In Vad Animal Models and Vad Patientsmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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“…Also, functional nACh receptors in some amygdala nuclei (like the basolateral complex) are predominantly 7-containing receptors [22]. These receptors are believed to play an antiinflammatory and neuroprotective role in neurodegenerative diseases and in stressful situations [23][24][25]. Concerning these observations, the aim of this work was to determine the density of 7 nicotinic receptors in the hippocampus, cortex and amygdala of rats submit-ted to the infusion of A peptide and correlate this with sustained attention.…”

Section: Introductionmentioning

confidence: 99%

Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain

Viel

Caetano²,

Albuquerque³

et al. 2012

CAR

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2012Chronic infusion of amyloid-peptide and sustained attention altered 7 nicotinic receptor density in the rat brain Current Alzheimer Research, Sharjah, v. 9, n. 10, supl., Part 2, pp. 1210-1220, dec, 2012 Abstract: It is already known that progressive degeneration of cholinergic neurons in brain areas such as the hippocampus and the cortex leads to memory deficits, as observed in Alzheimer's disease. This work verified the effects of the infusion of amyloid-(A ) peptide associated to an attentional rehearsal on the density of 7 nicotinic cholinergic receptor (nAChR) in the brain of male Wistar rats. Animals received intracerebroventricular infusion of A or vehicle (control -C) and their attention was stimulated weekly (Stimulated A group: S-A and Stimulated Control group: SC) or not (NonStimulated A group: N-SA and Non-Stimulated Control group: N-SC), using an active avoidance apparatus. Conditioned avoidance responses (CAR) were registered. Chronic infusion of A caused a 37% reduction in CAR for N-SA . In S-A , this reduction was not observed. At the end, brains were extracted and autoradiography for 7 nAChR was conducted using [125 I]--bungarotoxin. There was an increase in 7 density in hippocampus, cortex and amygdala of SA animals, together with the memory preservation. In recent findings from our lab using mice infused with A and the 7 antagonist methyllycaconitine, and stimulated weekly in the same apparatus, it was observed that memory maintenance was abolished. So, the increase in 7 density in brain areas related to memory might be related to a participation of this receptor in the long-lasting change in synaptic plasticity, which is important to improve and maintain memory consolidation.

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Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Cited by 83 publications

References 149 publications

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain

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Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Cited by 83 publications

References 149 publications

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Chronic Infusion of Amyloid-&beta; Peptide and Sustained Attention Altered &alpha;7 Nicotinic Receptor Density in the Rat Brain

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Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain