The Myelin Mutant Rat Taiep as a Model of Neuroimmunological Disease

Abstract

Taiep rat is a myelin mutant with a progressive motor syndrome characterized by tremor, ataxia, immobility episodes, epilepsy and paralysis of the hind limbs. The rats show an initial hypomyelination, followed by a progressive demyelination of the central nervous system, but not peripheral nerves. All myelin alterations are due to an accumulation of microtubules in the cytoplasm and their process in oligodendrocytes, which disrupt the transporting mechanism from endoplasmic reticulum to Cis portion of the Golgi apparatus. Because of these microtubule alterations, all major myelin proteins decreased progressively. In fact, several brain regions of taiep rats showed an increment in the expression of glial fibrillary acidic protein (GFAP) suggesting glia activation. Additionally, when glial cells from taiep rats were cultured and exposed to lipopolysaccharide (LPS) or interferon gamma (IFN)-gamma, they produced higher amounts of nitrites and nitrates than control glial cells, suggesting an activation of glia cells in taiep rats. There are also an activation of interleukins and changes in their receptors that correlated with the progressive demyelination in this myelin mutant. The activation of immune responses in older rats correlated with the electrophysiological alterations such as changes in the sleep-wake pattern and absence seizures, or locomotion pattern and ataxia. Additionally, the frequency and mean duration of immobility episodes (IE's) increased after 6 month of age, which is an expression of rapid eye movement (REM) sleep alteration, suggesting that taiep rats suffer of narcolepsy-cataplexy. These results clearly showed that taiep rats are suitable model of neuro-immune alterations associated to chronic demyelination, and it is alternative model to experimental allergic encephalomyelitis to study glia-neuron interaction. In conclusion, taiep rat showed progressive immunological, electrophysiological and behavioral alterations due to demyeli- nation associated with normal lifespan that allow us to do diverse studies from different approaches.