title: Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons.
abstract: Recent studies have demonstrated that human tau can be secreted by neurons and non-neuronal cells, an event linked to the propagation of tau pathology in the brain. In the present study, we confirmed that under physiological conditions, one tau-positive band was detected in the culture medium with an anti-tau antibody recognizing total tau and the Tau-1 antibody directed against unphosphorylated tau. We then examined whether tau secretion was modified upon insults. Tau secretion was increased by starvation [Earle's Balanced Salt Solution (EBSS)], inhibition of lysosomal function (leupeptin) and when both of these conditions were superimposed, this combined treatment having the most important effects on tau secretion. Interestingly, the pattern of tau secretion was distinct from that of control neurons when neurons were treated either with EBSS alone or EBSS + leupeptin. In these conditions, three tau-positive bands were detected in the culture medium. Two of these three bands were immunoreactive to Tau-1 antibody revealing that at least two tau species were released upon these treatments. Collectively, our results indicate that insults such as nutrient deprivation and lysosomal dysfunction observed in neurodegenerative diseases could result in an increase of tau secretion and propagation of tau pathology in the brain.
authors.affiliation: Département de Neurosciences, Université de Montréal, C.P.6128, Succ. Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Nguyen-Vi
authors.initials: NV
authors.lastname: Mohamed
authors.affiliation: Département de Neurosciences, Université de Montréal, C.P.6128, Succ. Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Plouffe
authors.affiliation: Département de Neurosciences, Université de Montréal, C.P.6128, Succ. Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Gaudeline
authors.initials: G
authors.lastname: Rémillard-Labrosse
authors.affiliation: Centre Hospitalier de l'Université Laval, Neurosciences, RC-9800, 2705 Boulevard Laurier Québec (QC), Canada, G1V 4G2.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
authors.affiliation: Département de Neurosciences, Université de Montréal, C.P.6128, Succ. Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Nicole
authors.initials: N
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003470:Culture Media; D007976:Leupeptins / Q000502:physiology; D008247:Lysosomes / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D003470:Culture Media; D007976:Leupeptins; C558298:Mapt protein, mouse; D016875:tau Proteins; C032854:leupeptin