A tight relationship between Amyloid-beta (Aβ) and α7-nicotinic Acetylcholine Receptors (α7-nAChRs) has been described in physiological conditions and in diseases characterized by cognitive impairment, such as Alzheimer’s disease. However, results are controversial because Aβ is likely to exert an agonistic or antagonistic effect on α7-nAchRs in a dose-dependent fashion. We have previously demonstrated that low concentrations of Aβ (200 pM), resembling the physiological content in the healthy brain, modulate the late phase of long-term potentiation (L-LTP) and memory through α7-nAchRs. Here, we studied whether endogenous α7-nAchRs are needed for 200 pM Aβ to modify a form of short-term plasticity, i.e. paired-pulse facilitation (PPF), and the early phase of LTP (E-LTP). Experiments were performed on mouse hippocampal slices of wild type (WT) and α7-nAchRs knock out (α7-KO) mice by field potential recordings at CA3-CA1 synapses. We demonstrated that α7-KOmice treated with 200 pM Aβ did not show the decrease of PPF and the conversion from E-LTP in L-LTP after a weak tetanic stimulation compared to slices from WT mice. These results were confirmed by a pharmacological blockage of α7-nAchRs by the selective antagonist methyllycaconitine (MLA). Thus, endogenous α7-nAchRs are needed for Aβ to exert its positive effects on PPF, an index of neurotransmitter release, and to convert E-LTP in L-LTP.

The effect of 200 pM Amyloid-beta on short- and long-term plasticity depends upon endogenous α7-nicotinic ACh receptors

Gulisano W;Puzzo D;Palmeri A
2017

Abstract

A tight relationship between Amyloid-beta (Aβ) and α7-nicotinic Acetylcholine Receptors (α7-nAChRs) has been described in physiological conditions and in diseases characterized by cognitive impairment, such as Alzheimer’s disease. However, results are controversial because Aβ is likely to exert an agonistic or antagonistic effect on α7-nAchRs in a dose-dependent fashion. We have previously demonstrated that low concentrations of Aβ (200 pM), resembling the physiological content in the healthy brain, modulate the late phase of long-term potentiation (L-LTP) and memory through α7-nAchRs. Here, we studied whether endogenous α7-nAchRs are needed for 200 pM Aβ to modify a form of short-term plasticity, i.e. paired-pulse facilitation (PPF), and the early phase of LTP (E-LTP). Experiments were performed on mouse hippocampal slices of wild type (WT) and α7-nAchRs knock out (α7-KO) mice by field potential recordings at CA3-CA1 synapses. We demonstrated that α7-KOmice treated with 200 pM Aβ did not show the decrease of PPF and the conversion from E-LTP in L-LTP after a weak tetanic stimulation compared to slices from WT mice. These results were confirmed by a pharmacological blockage of α7-nAchRs by the selective antagonist methyllycaconitine (MLA). Thus, endogenous α7-nAchRs are needed for Aβ to exert its positive effects on PPF, an index of neurotransmitter release, and to convert E-LTP in L-LTP.
α7-nAChRs; Amyloid-beta; Alzheimer's disease
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/317394
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