Regional distribution of nicotinic receptor subunit mRNAs in human brain: comparison between Alzheimer and normal brain

Hellström‐Lindahl, Ewa; Mousavi, Malahat; Zhang, Xiao; Ravid, R.; Nordberg, Agneta

doi:10.1016/s0169-328x(99)00030-3

Cited by 189 publications

(128 citation statements)

References 39 publications

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“…Although the protein loss is evident in AD, reductions in gene expression at the transcriptional level are less clear. The 36% reduction in alpha7nAChR-protein levels in the hippocampus of patients with AD (Guan et al, 2000) contrast with the 65% increase in alpha7nAChR-mRNA expression reported (Hellstrom-Lindahl et al, 1999). Apparent contradictory results were also found in the frontal cortex of AD patients showing no differences in [I 125 ] α-bungarotoxin binding (Davies and Feisullin, 1981;Sugaya et al, 1990), or a significant reduction of the alpha7nAChR-protein expression levels (Engidawork et al, 2001).…”

Section: Cholinergic Implications In Neurodegenerative Disorders: Fromentioning

confidence: 95%

Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Conejero-Goldberg

Davies

Ulloa

2008

Neuroscience & Biobehavioral Reviews

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Alzheimer's disease (AD) is the leading cause of dementia affecting over 25 million people worldwide. Classical studies focused on the description and characterization of the pathological hallmarks found in AD patients including the neurofibrillary tangles and the amyloid plaques. Current strategies focus on the etiology of these hallmarks and the different mechanisms contributing to neurodegeneration. Among them, recent studies reveal the close interplay between the immunological and the neurodegenerative processes. This article examines the implications of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) as a critical link between inflammation and neurodegeneration in AD. Alpha7nAChRs are not only expressed in neurons but also in Glia cells where they can modulate the immunological responses contributing to AD. Successful therapeutic strategies against AD should consider the connections between inflammation and neurodegeneration. Among them, alpha7nAChR may represent a pharmacological target to control these two mechanisms during the pathogenesis of neurodegenerative and behavioral disorders.

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Section: Cholinergic Implications In Neurodegenerative Disorders: Fromentioning

confidence: 95%

Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Conejero-Goldberg

Davies

Ulloa

2008

Neuroscience & Biobehavioral Reviews

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“…Evidence for this stems from the results of in situ hybridization and RT-PCR studies which demonstrate the presence of multiple nAChR transcripts including α3, α4, α7, and β2 mRNAs, with the others not yet investigated [91][92][93][94]. Radioligand binding studies show that 125 I-epibatidine, 3 Hnicotine, 125 I-A85380, 125 I-α-bungarotoxin and 125 I-α-conotoxinMII all bind to human striatum suggesting the presence of nAChRs containing the α4, α3 and/or α6, α7, and β2 [89,90,[95][96][97][98][99][100][101][102][103][104].…”

Section: Humansmentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

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“…In general, regions with high-to moderate-density of α7 nAChR gene expression and [ 125 I]α-BGT binding are related to learning and memory such as thalamic and hippocampal structures, the horizontal limb of the diagonal band of Broca, and the nucleus basalis of Meynert (Alkondon et al, 2007;Breese et al, 1997;FabianFine et al, 2001;Hellström-Lindahl et al, 1999;Schulz et al, 1991;Spurden et al, 1997). However, species differences exist regarding the total number of binding sites of α7 nAChR specific radioligands (Han et al, 2003) with for example a lower amount of [ 125 I]α-BGT binding in the monkey hippocampus or the human thalamus and cortex compared with the same regions of rat brain ) (Tab.…”

Section: Acknowledgementmentioning

confidence: 99%

“…During the last decade, comparable results were obtained by analysing other neurodegenerative diseases. Lewy body dementia (DLB) and Parkinson´s disease have also been associated with alterations in the transcription or translation of the α7 subunit (Burghaus et al, 2003;Court et al, 2000;Nordberg, 2001;Wevers & Schröder, 1999), indicating a hypocholinergic tone due to for example reduced levels of α7 mRNA and protein in the hippocampus and reticular nucleus in AD and DLB (Court et al, 1999;Guan et al, 2000;Hellström-Lindahl et al, 1999). Functional interactions of β-amyloid with α7 nAChR, revealed in vitro , and the colocalization of both in AD support the hypothesis that neuronal degeneration in AD might also be triggered by β-amyloidinitiated and α7 nAChR-mediated inflammatory processes (Bencherif & Lippiello, 2010).…”

Section: Alterations Of 7 Nachr In Diseased Brainmentioning

confidence: 99%

Neuroimaging - Clinical Applications

Bright¹

2012

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Regional distribution of nicotinic receptor subunit mRNAs in human brain: comparison between Alzheimer and normal brain

Cited by 189 publications

References 39 publications

Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Nicotinic receptors as CNS targets for Parkinson's disease

Neuroimaging - Clinical Applications

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