期刊
FRONTIERS IN AGING NEUROSCIENCE
卷 6, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2014.00166
关键词
beta-amyloid; dopamine release; nicotinic receptors; muscarinic receptors; Alzheimer's disease
资金
- Italian MIUR [2009R7WCZS_003]
- University of Genoa
- Alzheimer's Association [NIRG-11-205183]
Contradictory results have been reported on the Interaction of beta-amyloid (A beta) with cholinergic receptors. The present paper investigates the modulatory effect of A beta 1-40 on the neurotransmitter release evoked by nicotinic (nAChRs) and muscarinic (mAChRs) receptors. A beta 1-40 inhibits both nicotinic and muscarinic-evoked [H-3]DA overflow from rat nerve endings. Added to perfusion medium, A beta 1-40 is able to enter into synaptosomes; it exerts its inhibitory effect at extracellular sites when release is stimulated by nAChRs and intracellularly when release is evoked by mAChRs. Moreover, our data show that A beta 1-40 acts as non competitive antagonist of heteromeric alpha 4 beta 2* but not of alpha 3 beta 4* nAChRs which modulate [H-3]NA overflow. Positive allosteric modulators of nAChRs counteract its inhibitory effect. It might be that compounds of this type could be useful to prevent, slow down the appearance or reverse the cognitive decline typical of the normal processes of brain aging.
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