Cuprizone does not induce CNS demyelination in nonhuman primates

Abstract

Cognitive decline is a common symptom in multiple sclerosis patients, with profound effects on the quality of life. A nonhuman primate model of multiple sclerosis would be best suited to test the effects of demyelination on complex cognitive functions such as learning and reasoning. Cuprizone has been shown to reliably induce brain demyelination in mice. To establish a nonhuman primate model of multiple sclerosis, young adult cynomolgus monkeys were administered cuprizone per os as a dietary supplement. The subjects received increasing cuprizone doses (0.3–3% of diet) for up to 18 weeks. Magnetic resonance imaging and immunohistological analyses did not reveal demyelination in these monkeys.

Teriflunomide as a therapeutic means for myelin repair

“…The following primary antibodies were used: mouse anti-APC (CC1, 1:300, Sigma-Aldrich, Cat# OP80, RRID:AB_ 2057371); rabbit anti-sex determining region Y-Box 10 (Sox10; 1:100, DCS Immunoline, Hamburg, Germany Cat# S1058C002, RRID: AB_2313583) and goat anti-Sox10 (1:200, R&D System, Minneapolis, US Cat# AF2864; RRID: AB_442208); rat anti-proteolipid protein (PLP, 1:250, kind gift from B. Trapp and R. Dutta, Dept. of Neurosciences, Cleveland Clinic, OH, [ 22 ]), mouse anti-mammalian Achaete scute homolog-1 (Mash1, 1:200; [ 23 , 24 ]) and rabbit anti-mitochondrial outer membrane marker (Tom20; Santa Cruz, Heidelberg, Germany Cat# sc-11415 (FL-145), RRID: AB_2207533). Slices were then washed twice in 1 × TBS for 5 min each and secondary antibodies were diluted 1:200 and applied for 30 min along with 4′,6-diamidino-2-phenylindol (DAPI, 1:50) in PBS.…”

Identification of novel myelin repair drugs by modulation of oligodendroglial differentiation competence

“…The following primary antibodies were used: mouse anti-APC (CC1, 1:500, GeneTex Cat# GTX16794, RRID:AB_422,404), rabbit anti-glutathione-S-transferase pi (GSTpi, 1:2000, Enzo Life Sciences, Farmingdale, NY, US Cat# ADI-MSA-101-E, RRID:AB_2,039,147), goat anti-PDGFR (alpha/CD140A, 1:250, Neuromics, Edina, MN, US Cat# GT15150, RRID:AB_2,737,233), and rat anti-PLP [PLP, 1:250, kind gift from B. Trapp and R. Dutta, Dept. of Neurosciences, Cleveland Clinic, OH, USA [36] . Slices were then washed twice in 1x TBS for five minutes each and secondary antibodies were diluted 1:200 and applied for 30 minutes along with DAPI (1:50) in PBS.…”

Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination

“…Interestingly, in experiments using hamsters the cuprizone concentration needed to be increased to 3% or even 5%—compared to 0.2%—0.5% in experiments on mice or rat—to induce brain alterations. One very small study using non-human primates did not find brain demyelination in young cynomolgus macaques even after 18 weeks on a 3% cuprizone diet [ 38 ]. However, the lack of demyelination could be because even higher, but untested, doses of cuprizone are needed to induce demyelination in macaques.…”