APP（SWE）转基因小鼠中的选择性烟碱受体后果。

Selective nicotinic receptor consequences in APP(SWE) transgenic mice.

作者信息

Bednar Ivan, Paterson David, Marutle Amelia, Pham Therese M, Svedberg Marie, Hellström-Lindahl Ewa, Mousavi Malahat, Court Jennifer, Morris Christopher, Perry Elaine, Mohammed Abdul, Zhang Xiao, Nordberg Agneta

机构信息

Divisions of Molecular Neuropharmacology, Occupational Therapy and Elderly Care Research (NEUROTEC), S-141 86 Stockholm, Sweden.

出版信息

Mol Cell Neurosci. 2002 Jun;20(2):354-65. doi: 10.1006/mcne.2002.1112.

DOI:10.1006/mcne.2002.1112

PMID:12093166

Abstract

The nicotinic (nAChRs) and muscarinic (mAChRs) acetylcholine receptors and acetylcholinesterase (AChE) activity were studied in the brains of APP(SWE) transgenic mice (Tg+) and age-matched nontransgenic controls (Tg-) that were between 4 and 19 months of age. A significant increase in the binding of 125I-labeled alpha-bungarotoxin (alpha7 nAChRs) was observed in most brain regions analyzed in 4-month-old Tg+ mice, preceding learning and memory impairments and amyloid-beta (Abeta) pathology. The enhanced alpha7 receptor binding was still detectable at 17-19 months of age. Increase in [3H]cytisine binding (alpha4beta2 nAChRs) was measured at 17-19 months of age in Tg+ mice, at the same age when the animals showed heavy Abeta pathology. No significant changes in [3H]pirenzepine (M1 mAChRs) or [3H]AFDX 384 (M2 mAChRs) binding sites were found at any age studied. The upregulation of the nAChRs probably reflects compensatory mechanisms in response to Abeta burden in the brains of Tg+ mice.

摘要

在4至19月龄的APP(SWE)转基因小鼠(Tg+)和年龄匹配的非转基因对照小鼠(Tg-)的大脑中，研究了烟碱型(nAChRs)和毒蕈碱型(mAChRs)乙酰胆碱受体以及乙酰胆碱酯酶(AChE)的活性。在4月龄Tg+小鼠的大多数分析脑区中，观察到125I标记的α-银环蛇毒素(α7 nAChRs)结合显著增加，这发生在学习和记忆障碍及β淀粉样蛋白(Aβ)病理改变之前。在17 - 19月龄时，仍可检测到α7受体结合增强。在17 - 19月龄的Tg+小鼠中，检测到[3H]胞嘧啶结合(α4β2 nAChRs)增加，此时动物出现严重的Aβ病理改变。在所研究的任何年龄，[3H]哌仑西平(M1 mAChRs)或[3H]AFDX 384(M2 mAChRs)结合位点均未发现显著变化。nAChRs的上调可能反映了Tg+小鼠大脑对Aβ负荷的代偿机制。