Advanced Plo Theory Tom Chambers Pdf Download BETTER

Microfluidic chambers facilitate the isolation of axonal terminals from cell bodies in culture modelling pathology along the neuron from synapse to soma. Several studies have shown that degeneration may start in the striatal axons before affecting the cell soma of dopaminergic neurons33. In support of this theory, neuroimaging studies have shown that human PD presents early with a larger loss of transporters and other DA axon markers in the striatum than in the SNc34,35. As a result several groups have studied this early degeneration in α-syn overexpression mouse models and shown early striatal synaptic and dopamine release defects prior to neurodegeneration12,36. It is therefore important to investigate in vitro and in vivo whether the toxic effects of α-syn on axon terminals can be alleviated with CLR01 administration. Using microfluidic chambers in vitro, we observed that CLR01 reduced the accumulation of α-syn oligomers in the cell soma after treatment of axonal terminals, although it is possible that this was in part due to an inhibition of retrograde transport of α-syn, or to the minimal flow of CLR01-containing medium to the insult chamber. In parallel studies in vivo, CLR01 administration reduced lesions in dopaminergic cell somas in the SNc after injection of mPFFs to the dorsal striatum, confirming a protective effect of CLR01 against α-syn pathology in both axons and cell bodies.

advanced plo theory tom chambers pdf download