title: Dimethyl sulfoxide induces both direct and indirect tau hyperphosphorylation.
abstract: Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser(202)/Thr(205)), PHF-1 (Ser(396)/Ser(404)) and AT180 (Thr(231)) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro.
authors: Département de Neurosciences et Psychiatrie, Faculté de Médecine, Université Laval, Québec, Québec, Canada. carl.julien@crchul.ulaval.ca
authors: Carl
authors: C
authors: Julien
authors: François
authors: F
authors: Marcouiller
authors: Alexis
authors: A
authors: Bretteville
authors: Noura B
authors: NB
authors: El Khoury
authors: Joanie
authors: J
authors: Baillargeon
authors: Sébastien S
authors: SS
authors: Hébert
authors: Emmanuel
authors: E
authors: Planel
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D045744:Cell Line, Tumor; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase; D010749:Phosphoprotein Phosphatases; D004121:Dimethyl Sulfoxide