α7 Nicotinic Receptor Up-regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease

Counts, Scott; He, Bin; Che, Shaoli; Ikonomović, Miloš D.; DeKosky, Steven T.; Ginsberg, Stephen D.; Mufson, Elliott J.

doi:10.1001/archneur.64.12.1771

Cited by 98 publications

(101 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, a7 nAChR expression was increased by approximately 50% in both AD/GAL-and AD/GAL+ cells relative to NCI cells ( fig. 1 b), similar to previous observations in mild/moderate AD [14] .…”

Section: Resultssupporting

confidence: 92%

Galanin Hyperinnervation Upregulates Choline Acetyltransferase Expression in Cholinergic Basal Forebrain Neurons in Alzheimer’s Disease

Counts

Che

et al. 2008

Neurodegener Dis

Self Cite

View full text Add to dashboard Cite

Background: Fibers containing galanin (GAL) enlarge and hyperinnervate cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons in late-stage Alzheimer’s disease (AD), yet the physiological consequences of this phenomenon are unclear. Objective: To determine whether GAL hyperinnervation of cholinergic NB neurons modulates the expression of genes critical to cholinergic transmission [e.g. acetylcholine (ACh) metabolism and ACh receptors] in AD. Methods: Single-cell gene expression profiling was used to compare cholinergic mRNA levels in non-GAL-hyperinnervated NB neurons in tissue autopsied from cases classified as having no cognitive impairment (NCI) or late-stage AD (AD/GAL–) and in GAL-hyperinnervated (AD/GAL+) NB neurons from the same AD subjects. Results: AD/GAL+ cells displayed a significant upregulation in choline acetyltransferase (ChAT) mRNA expression compared to NCI and AD/GAL– cells. Conclusion: GAL fiber hyperinnervation of cholinergic NB neurons upregulates the expression of ChAT, the synthetic enzyme for ACh, suggesting that GAL regulates the cholinergic tone of CBF neurons in AD.

show abstract

Section: Resultssupporting

confidence: 92%

Galanin Hyperinnervation Upregulates Choline Acetyltransferase Expression in Cholinergic Basal Forebrain Neurons in Alzheimer’s Disease

Counts

Che

et al. 2008

Neurodegener Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Increased intracellular Ca 2ϩ can lead to cell death and has been associated with neuronal death in neurodegenerative diseases (35). Along these lines, overexpression of ␣7-nAChRs has been shown to play a role in neurological disorders (36). Studies have shown that in neuronal cultures, gp120 can induce an increase in Ca 2ϩ levels, leading to neuronal injury, an effect that can be blocked with memantine (37).…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of the Neuronal Nicotinic Receptor α7 by HIV Glycoprotein 120

Ballester

Capó-Vélez

García-Beltrán

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Approximately 30 -50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV ؉ individuals, including neuroinflammation mediated by infected microglia and neuronal toxicity by HIV proteins. A key protein associated with the neurological complications of HIV, gp120, forms part of the viral envelope and can be found in the CSF of infected individuals. HIV-1-gp120 interacts with several receptors including CD4, CCR5, CXCR4, and nicotinic acetylcholine receptors (nAChRs). However, the role of nAChRs in HIV-associated neurocognitive disorder has not been investigated. We studied the effects of gp120 IIIB on the expression and function of the nicotinic receptor ␣7 (␣7-nAChR). Our results show that gp120, through activation of the CXCR4 chemokine receptor, induces a functional up-regulation of ␣7-nAChRs. Because ␣7-nAChRs have a high permeability to Ca 2؉ , we performed TUNEL staining to investigate the effects of receptor up-regulation on cell viability. Our data revealed an increase in cell death, which was blocked by the selective antagonist ␣-bungarotoxin. The in vitro data are supported by RT-PCR and Western blot analysis, confirming a remarkable up-regulation of the ␣7-nAChR in gp120-transgenic mice brains. Specifically, ␣7-nAChR up-regulation is observed in mouse striatum, a region severely affected in HIV ؉ patients. In summary, CXCR4 activation induces up-regulation of ␣7-nAChR, causing cell death, suggesting that ␣7-nAChR is a previously unrecognized contributor to the neurotoxicity associated with HIV infection.

show abstract

“…Appropriate caution must however be maintained, because false positives might be generated when evaluating protein expression using commercially available antibodies (Herber et al, 2004;Jones and Wonnacott, 2005). Experiments conducted with competitive antagonists such as a-Btx or MLA have found opposing results: an increase in expression of a7 nAChRs thought to compensate for the loss of ACh in AD (Counts et al, 2007;Liu et al, 2013) and reduced expression of a7 nAChRs in other studies (Burghaus et al, 2000). A lower level of a7 nAChR expression on neurons, at the same time as expression was higher on astrocytes, was also reported in sporadic and familial AD (Yu et al, 2005).…”

Section: A Alzheimer's Diseasementioning

confidence: 99%