Inhibition of LTP by beta-amyloid is prevented by activation of β2 adrenoceptors and stimulation of the cAMP/PKA signalling pathway

Abstract 

Beta-amyloid (Aβ) is the main component of the extracellular plaques present in patients with Alzheimer's disease (AD) and studies have shown that exogenous application of Aβ results in neurodegeneration. As a model of the neurodegenerative action of Aβ, we have previously shown that acutely applied Aβ inhibits the induction of LTP in the hippocampus in vitro. In the present studies, we have studied the effect of β-adrenoceptor activation on the Aβ inhibition of LTP. Pharmacological activation of β2 adrenoceptors, but not of β1 adrenoceptors, was found to prevent the Aβ evoked inhibition of LTP in the dentate gyrus of adult animals. The prevention of the effect of Aβ was shown to occur via the cAMP/PKA signaling pathway as the adenylate cyclase-stimulating agent forskolin prevented the Aβ inhibition of LTP, an action prevented by the PKA inhibitor, Rp-8-Br-cAMPs. We suggest microglia as a likely site of action of the neuroprotective effect of β2 adrenoceptor activation. Therapeutic treatment for AD may include agents that activate β2 receptors and elevate cAMP.

Keywords: Beta-amyloid, Alzheimer's disease, Noradrenaline, PKA, LTP, Hippocampus