Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology

Teaktong, Thanasak; Graham, Alison; Court, Jennifer A.; Perry, Robert H.; Jaros, Evelyn; Johnson, Mary; Hall, Richard S.; Perry, Elaine K.

doi:10.1016/j.jns.2004.06.015

Cited by 52 publications

(21 citation statements)

References 49 publications

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“…The ␣7nAChR has also been implicated in AD (51)(52)(53)(54), as expression of these receptors is either decreased or increased in AD brains (55,56) and animal models of AD (57). Furthermore, there is evidence that ␣7nAChR interacts with A␤ 1-42 oligomers (58,59).…”

Section: Journal Of Biological Chemistry 36547mentioning

confidence: 99%

Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1

Beraldo

Arantes

Santos

et al. 2010

Journal of Biological Chemistry

106

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The prion protein (PrP C ) is a conserved glycosylphosphatidylinositol-anchored cell surface protein expressed by neurons and other cells. Stress-inducible protein 1 (STI1) binds PrP C extracellularly, and this activated signaling complex promotes neuronal differentiation and neuroprotection via the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP-dependent protein kinase 1 (PKA) pathways. However, the mechanism by which the PrP C -STI1 interaction transduces extracellular signals to the intracellular environment is unknown. We found that in hippocampal neurons, STI1-PrP C engagement induces an increase in intracellular Ca 2؉ levels. This effect was not detected in PrP C -null neurons or wild-type neurons treated with an STI1 mutant unable to bind PrP C . Using a best candidate approach to test for potential channels involved in Ca 2؉ influx evoked by STI1-PrP C , we found that ␣-bungarotoxin, a specific inhibitor for ␣7 nicotinic acetylcholine receptor (␣7nAChR), was able to block PrP C -STI1-mediated signaling, neuroprotection, and neuritogenesis. Importantly, when ␣7nAChR was transfected into HEK 293 cells, it formed a functional complex with PrP C and allowed reconstitution of signaling by PrP C -STI1 interaction. These results indicate that STI1 can interact with the PrP C ⅐␣7nAChR complex to promote signaling and provide a novel potential target for modulation of the effects of prion protein in neurodegenerative diseases.Prions are the infectious components of transmissible spongiform encephalopathies that can self-perpetuate by imprinting an anomalous conformation onto a glycosylphosphatidylinositol-anchored host protein known as the prion protein (PrP C ). 3Conversion of PrP C to the protease-resistant prion is thought to be a major event in prion diseases (1). However, despite the wealth of knowledge on prions, the roles of PrP C on synaptic function and neuronal health are still not completely understood. Studies in yeast, mammalian cells, and mouse models support the hypothesis that PrP C plays a major role in neuroprotection and neuronal differentiation (for review, see Refs. 1-3).In humans, the initial cognitive dysfunction observed in transmissible spongiform encephalopathies is remarkably similar to those observed in Alzheimer disease (AD). Therefore, synaptic failure is likely to play a major role in the cognitive alterations seen in these neurological disorders (4). For instance, in AD, the role for A␤ ligands in synaptic dysfunction has received considerable attention (5, 6). Interestingly, recent work provided evidence that PrP C functions as a receptor for A␤ and that this interaction mediates some of the effects of A␤ oligomers in synaptic plasticity (7) although these results are controversial at the moment (8, 9). Moreover, PrP C seems to regulate the ␤-secretase cleavage of amyloid precursor protein, thereby regulating the production of A␤ (10). In addition, ␣-secretase regulates the cleavage of PrP C , generating an N-terminal fragment with neuroprotective activity (11,12)...

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Section: Journal Of Biological Chemistry 36547mentioning

confidence: 99%

Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1

Beraldo

Arantes

Santos

et al. 2010

Journal of Biological Chemistry

106

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“…A major neuropathological feature of most patients with clinical AD is the loss of cholinergic neurons in the basal forebrain (Schliebs and Arendt 2006;Geula et al 2008), and several groups have reported a selective loss of different subtypes of acetylcholine receptors (AChRs) in AD brains (Wevers et al 2000;Teaktong et al 2004). By modulating activity-dependent events, AChRs participate in fundamental aspects of synaptic plasticity (Albuquerque et al 1997;Ge and Dani 2005).…”

Section: Cholinergic Mechanismsmentioning

confidence: 99%

Alzheimer’s Disease Amyloid β-Protein and Synaptic Function

et al. 2009

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Alzheimer's disease (AD) is characterized neuropathologically by the deposition of different forms of amyloid beta-protein (A beta) including variable amounts of soluble species that correlate with severity of dementia. The extent of synaptic loss in the brain provides the best morphological correlate of cognitive impairment in clinical AD. Animal research on the pathophysiology of AD has therefore focussed on how soluble A beta disrupts synaptic mechanisms in vulnerable brain regions such as the hippocampus. Synaptic plasticity in the form of persistent activity-dependent increases or decreases in synaptic strength provide a neurophysiological substrate for hippocampal-dependent learning and memory. Acute treatment with human-derived or chemically prepared soluble A beta that contains certain oligomeric assemblies, potently and selectively disrupts synaptic plasticity causing inhibition of long-term potentiation (LTP) and enhancement of long-term depression (LTD) of glutamatergic transmission. Over time these and related actions of A beta have been implicated in reducing synaptic integrity. This review addresses the involvement of neurotransmitter intercellular signaling in mediating or modulating the synaptic plasticity disrupting actions of soluble A beta, with particular emphasis on the different roles of glutamatergic and cholinergic mechanisms. There is growing evidence to support the view that NMDA and possibly nicotinic receptors are critically involved in mediating the disruptive effect of A beta and that targeting muscarinic receptors can indirectly modulate A beta's actions. Such studies should help inform ongoing and future clinical trials of drugs acting through the glutamatergic and cholinergic systems.

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“…In particular, decreased levels of α4 and α7 are observed in neurons of the temporal cortex and hippocampus; additionally, reduced levels of α4 are observed in neurons of the entorhinal cortex. On the other hand, increased levels of α7 are found in astrocytes of these brain areas, and this increment was correlated with the extent of neuritic plaques (Banerjee et al 2000;Teaktong et al 2003Teaktong et al , 2004Yu et al 2005). The decreased α7 expression in neurons may contribute to the reduced agonist binding to this subunit found in postmortem hippocampus (Hellstrom-Lindahl et al 1999).…”

Section: Disruption Of Cholinergic Neurotransmission and Attention Dementioning

confidence: 99%

Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme

Schaeffer

Gattaz

2008

Psychopharmacology

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Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology

Cited by 52 publications

References 49 publications

Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1

Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1

Alzheimer’s Disease Amyloid β-Protein and Synaptic Function

Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme

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