Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides
<p>Abstract</p> <p>Background</p> <p>β-amyloid (Aβ) accumulation is described as a hallmark of Alzheimer’s disease (AD). Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs), which are abundantly expr...
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://www.biomedcentral.com/1471-2202/13/155 |
| _version_ | 1811246678158606336 |
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| author | Liu Qiang Huang Yao Shen Jianxin Steffensen Scott Wu Jie |
| author_facet | Liu Qiang Huang Yao Shen Jianxin Steffensen Scott Wu Jie |
| author_sort | Liu Qiang |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>β-amyloid (Aβ) accumulation is described as a hallmark of Alzheimer’s disease (AD). Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7β2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aβ exposure. To extend our previous work, we evaluated the expression and pharmacology of α7β2-nAChRs in hippocampal interneurons and their sensitivity to Aβ.</p> <p>Results</p> <p>GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7β2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-β-erythroidine (DHβE), a nAChR β2* subunit selective blocker, and α7 and β2 subunit interaction using immunoprecipitation assay. In addition, α7β2-nAChRs were sensitive to 1 nM oligomeric Aβ. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice.</p> <p>Conclusion</p> <p>These findings suggest that Aβ modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7β2-nAChRs could be an early and critical event in Aβ-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.</p> |
| first_indexed | 2024-04-12T14:57:45Z |
| format | Article |
| id | doaj.art-27f5beb57af74916b348e65d44f5c40a |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-12T14:57:45Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-27f5beb57af74916b348e65d44f5c40a2022-12-22T03:28:11ZengBMCBMC Neuroscience1471-22022012-12-0113115510.1186/1471-2202-13-155Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptidesLiu QiangHuang YaoShen JianxinSteffensen ScottWu Jie<p>Abstract</p> <p>Background</p> <p>β-amyloid (Aβ) accumulation is described as a hallmark of Alzheimer’s disease (AD). Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7β2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aβ exposure. To extend our previous work, we evaluated the expression and pharmacology of α7β2-nAChRs in hippocampal interneurons and their sensitivity to Aβ.</p> <p>Results</p> <p>GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7β2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-β-erythroidine (DHβE), a nAChR β2* subunit selective blocker, and α7 and β2 subunit interaction using immunoprecipitation assay. In addition, α7β2-nAChRs were sensitive to 1 nM oligomeric Aβ. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice.</p> <p>Conclusion</p> <p>These findings suggest that Aβ modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7β2-nAChRs could be an early and critical event in Aβ-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.</p>http://www.biomedcentral.com/1471-2202/13/155Nicotinic acetylcholine receptorAmyloidHippocampal interneuronPatch-clampAcutely dissociated neuron |
| spellingShingle | Liu Qiang Huang Yao Shen Jianxin Steffensen Scott Wu Jie Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides BMC Neuroscience Nicotinic acetylcholine receptor Amyloid Hippocampal interneuron Patch-clamp Acutely dissociated neuron |
| title | Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides |
| title_full | Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides |
| title_fullStr | Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides |
| title_full_unstemmed | Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides |
| title_short | Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides |
| title_sort | functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides |
| topic | Nicotinic acetylcholine receptor Amyloid Hippocampal interneuron Patch-clamp Acutely dissociated neuron |
| url | http://www.biomedcentral.com/1471-2202/13/155 |
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