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Functional α7ß2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid ß peptides.
Liu, Qiang; Huang, Yao; Shen, Jianxin; Steffensen, Scott; Wu, Jie.
Afiliação
  • Liu Q; Divisions of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA.
BMC Neurosci ; 13: 155, 2012 Dec 29.
Article em En | MEDLINE | ID: mdl-23272676
BACKGROUND: ß-amyloid (Aß) accumulation is described as a hallmark of Alzheimer's disease (AD). Aß 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 α7ß2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aß exposure. To extend our previous work, we evaluated the expression and pharmacology of α7ß2-nAChRs in hippocampal interneurons and their sensitivity to Aß. RESULTS: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7ß2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-ß-erythroidine (DHßE), a nAChR ß2* subunit selective blocker, and α7 and ß2 subunit interaction using immunoprecipitation assay. In addition, α7ß2-nAChRs were sensitive to 1 nM oligomeric Aß. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. CONCLUSION: These findings suggest that Aß modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7ß2-nAChRs could be an early and critical event in Aß-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Peptídeos beta-Amiloides / Receptores Nicotínicos / Região CA1 Hipocampal / Neurônios GABAérgicos / Interneurônios Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: BMC Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Peptídeos beta-Amiloides / Receptores Nicotínicos / Região CA1 Hipocampal / Neurônios GABAérgicos / Interneurônios Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: BMC Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos