AI Article Synopsis
- Filamentous tau inclusions are linked to Alzheimer's disease and affect neuronal function, but how they impact synaptic transmission is not fully understood.
- Researchers injected human tau protein into squid axon terminals, revealing that tau can block synaptic transmission and cause aggregation of synaptic vesicles without altering calcium current.
- The study found that a neuro-protective agent, T-817MA, can reverse the synaptic issues caused by tau, highlighting new insights into tau's role in neurotoxicity and potential treatment options.
Article Abstract
Filamentous tau inclusions are hallmarks of Alzheimer's disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099362 | PMC |
| http://dx.doi.org/10.3389/fnsyn.2011.00003 | DOI Listing |
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