Curcumin protects organotypic hippocampal slice cultures 4 from Ab1–42 -induced synaptic toxicity

Increasing evidence demonstrates that beta-amyloid (Ab) is toxic to synapses, resulting in the progressive dismantling of neuronal circuits. Counteract the synaptotoxic effects of Ab could be particularly relevant for providing effective treatments for Alzheimer’s disease (AD). Curcumin was recently reported to improve learning and memory in animal models of AD. Little is currently known about the specific mechanisms by which Ab affects neuronal excitability and curcumin ameliorates synaptic transmission in the hippocampus. Organotypic hippocampal slice cultures exposed to Ab1–42 were used to study the neuroprotective effects of curcumin through a spectral analysis of multi-electrode array (MEA) recordings of spontaneous neuronal activity. Curcumin counteracted both deleterious effects of Ab; the initial synaptic dysfunction and the later neuronal death. The analysis of MEA recordings of spontaneous neuronal activity showed an attenuation of signal propagation induced by Ab before cell death and curcumin-induced alterations to local field potential (LFP) phase coherence. Curcumin-mediated attenuation of Ab-induced synaptic dysfunction involved regulation of synaptic proteins, namely phospho-CaMKII and phosphosynapsin I. Taken together, our results expand the neuroprotective role of curcumin to a synaptic level. The identification of these mechanisms underlying the effects of curcumin may lead to new targets for future therapies for AD.

Being and goodness

The old scholastic principle of the "convertibility" of being and goodness strikes nearly all moderns as either barely comprehensible or plain false. "Convertible" is a term of art meaning "interchangeable" in respect of predication, where the predicates can be exchanged salva veritate albeit not salva sensu: their referents are, as the maxim goes, really the same albeit conceptually different. The principle seems, at first blush, absurd. Did the scholastics literally mean that every being is good? Is that supposed to include a cancer, a malaria parasite, an earthquake that kills millions? If every being is good, then no being is bad—but how can that be? To the contemporary philosophical mind, such bafflement is understandable. It derives from the systematic dismantling of the great scholastic edifice that took place over half a millennium. With the loss of the basic concepts out of which that edifice was built, the space created by those concepts faded out of existence as well. The convertibility principle, like virtually all the other scholastic principles (not all, since some do survive and thrive in analytic philosophy), could not persist in a post-scholastic space wholly alien to it.