Cellular Expression of α7 Nicotinic Acetylcholine Receptor Protein in the Temporal Cortex in Alzheimer's and Parkinson's Disease—A Stereological Approach

Banerjee, Carolin; Nyengaard, Jens Randel; Wevers, Andrea; Vos, Rob A.I.de; Steur, Ernst N.H. Jansen; Lindstrom, Jon; Pilz, Kirsten; Nowacki, Sonja; Bloch, Wilhelm; Schröder, Hannsjörg

doi:10.1006/nbdi.2001.0409

Cited by 17 publications

(25 citation statements)

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“…In fact, α7 nAChR-selective agonists are unable to activate these receptors in APP transgenic mice and recent work on human AD postmortem tissue and indicate that much of the receptor protein is functionally inactivated due to association with Aβ peptide (Ren et al, 2007; Soderman et al, 2008; Wang et al, 2009); (Perry et al, 1978; Banerjee et al, 2000; Martin-Ruiz et al, 2000; Dineley et al, 2001; Dineley et al, 2002b; Teaktong et al, 2003; Counts et al, 2007; Ikonomovic et al, 2009; Yu et al, 2009). In contrast to its role in early AD, α7 nAChRs may actually contribute to the pathology of late-stage AD through deleterious effects on synaptic integrity, cholinergic functionality, and cognition.…”

Section: Discussionmentioning

confidence: 99%

“…In early AD, there is impairment in hippocampus-based episodic memory that is improved through enhancement of cholinergic transmission, indicating that hypoactivity of septo-hippocampal projections underlie the earliest AD symptomatology (Riekkinen et al, 1987), which appear to be via reductions in choline acetyltransferase (ChAT) activity as well as depletion of nicotinic acetylcholine receptors (nAChRs)(Perry et al, 1978; Banerjee et al, 2000; Pappas et al, 2000). …”

Section: Introductionmentioning

confidence: 99%

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Loss of α7 Nicotinic Receptors Enhances β-Amyloid Oligomer Accumulation, Exacerbating Early-Stage Cognitive Decline and Septohippocampal Pathology in a Mouse Model of Alzheimer's Disease

Hernandez¹,

Kayed²,

Zheng³

et al. 2010

J. Neurosci.

175

138

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Early Alzheimer's disease (AD) is marked by cholinergic hypofunction, neuronal marker loss, and decreased nicotinic acetylcholine receptor (nAChR) density from the cortex and hippocampus. ␣7 nAChRs expressed on cholinergic projection neurons and target regions have been implicated in neuroprotection against ␤-amyloid (A␤) toxicity and maintenance of the septohippocampal phenotype. We tested the role that ␣7 nAChRs perform in the etiology of early AD by genetically deleting the ␣7 nAChR subunit from the Tg2576 mouse model for AD and assessing animals for cognitive function and septohippocampal integrity. Thus, Tg2576 mice transgenic for mutant human amyloid precursor protein (APP) were crossed with ␣7 nAChR knock-out mice (A7KO) to render an animal with elevated A␤ in the absence of ␣7 nAChRs (A7KO-APP). We found that learning and memory deficits seen in 5-month-old APP mice are more severe in the A7KO-APP animals. Analyses of animals in early-stage preplaque cognitive decline revealed signs of neurodegeneration in A7KO-APP hippocampus as well as loss of cholinergic functionality in the basal forebrain and hippocampus. These changes occurred concomitant with the appearance of a dodecameric oligomer of A␤ that was absent from all other genotypic groups, generating the hypothesis that increased soluble oligomeric A␤ may underlie additional impairment of A7KO-APP cognitive function. Thus, ␣7 nAChRs in a mouse model for early-stage AD appear to serve a neuroprotective role through maintenance of the septohippocampal cholinergic phenotype and preservation of hippocampal integrity possibly through influences on A␤ accumulation and oligomerization.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss of α7 Nicotinic Receptors Enhances β-Amyloid Oligomer Accumulation, Exacerbating Early-Stage Cognitive Decline and Septohippocampal Pathology in a Mouse Model of Alzheimer's Disease

Hernandez¹,

Kayed²,

Zheng³

et al. 2010

J. Neurosci.

175

138

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“…Loss of nAChRs has been reported in patients with diverse forms of dementia [45]. In particular, a reduction in α7 subunit number was detected in AD and PD brain tissue specimens [46]. The administration of ligands targeting nicotinic receptors in animal models of neurodegeneration, as well as in humans, induced cognitive improvement [47] and conferred neuroprotection against several neurotoxic agents [48,49].…”

Section: Discussionmentioning

confidence: 99%

Untitled

Simone

Ajmone‐Cat

Carnevale

et al. 2005

J Neuroinflammation

214

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Background: Nicotinic acetylcholine (Ach) receptors are ligand-gated pentameric ion channels whose main function is to transmit signals for the neurotransmitter Ach in peripheral and central nervous system. However, the α7 nicotinic receptor has been recently found in several non-neuronal cells and described as an important regulator of cellular function. Nicotine and ACh have been recently reported to inhibit tumor necrosis factor-α (TNF-α) production in human macrophages as well as in mouse microglial cultures. In the present study, we investigated whether the stimulation of α7 nicotinic receptor by the specific agonist nicotine could affect the functional state of activated microglia by promoting and/or inhibiting the release of other important proinflammatory and lipid mediator such as prostaglandin E 2 .

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“…Global density of AchR is increased in the globus pallidus (Griffiths et al 1990) and decreased in the striatum (Gotti et al 2006) where nicotinic AchR density (Court et al 2000), more particularly the density of the a4-, a6-, b2-, and b3-subunits (Gotti et al 2006), is also reduced. Decreased levels of a4and a7subunits were also observed in cortical regions (Banerjee et al 2000;Burghaus et al 2003). For the muscarinic receptors, contradictory results were observed in the putamen (Ahlskog et al 1991;Griffiths et al 1994) while increased density of the M2 muscarinic receptor was reported in cortical structures (Rinne et al 1989).…”

Section: Neurotransmitters and Neurotrophic Factorsmentioning

confidence: 97%

“…Decreased levels of α4‐ and α7‐subunits were also observed in cortical regions (Banerjee et al . ; Burghaus et al . ).…”

Section: Neurotransmitters and Neurotrophic Factorsmentioning

confidence: 99%

Molecular changes in the postmortem parkinsonian brain

Toulorge

Schapira²,

Hajj

2016

Journal of Neurochemistry

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Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by 'reverse biochemistry' i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD.

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Cellular Expression of α7 Nicotinic Acetylcholine Receptor Protein in the Temporal Cortex in Alzheimer's and Parkinson's Disease—A Stereological Approach

Cited by 17 publications

References 0 publications

Loss of α7 Nicotinic Receptors Enhances β-Amyloid Oligomer Accumulation, Exacerbating Early-Stage Cognitive Decline and Septohippocampal Pathology in a Mouse Model of Alzheimer's Disease

Loss of α7 Nicotinic Receptors Enhances β-Amyloid Oligomer Accumulation, Exacerbating Early-Stage Cognitive Decline and Septohippocampal Pathology in a Mouse Model of Alzheimer's Disease

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Molecular changes in the postmortem parkinsonian brain

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