Binding of microtubules to transitional elements in oligodendrocytes of the myelin mutanttaiep rat

Abstract

The presence of microtubules physically bound to smooth endoplasmic reticulum profiles of oligodendrocytes constitutes the most conspicuous feature observed in the myelin mutant taiep rat. The endoplasmic reticulum membranes associated with microtubules were morphologically characterized as transitional elements that constitute the intermediate compartment according to their topographic location close to the cis‐Golgi apparatus. The development of this surprising microtubular defect appears to be associated with the early events of myelination. Transitional elements associated with microtubules operate in protein transport from endoplasmic reticulum to cis‐Golgi. This microtubular defect could explain the dysmyelination and neurologic alterations observed in taiep rats. Moreover, these findings allow us to propose that there is a blockage of protein traffic at the intermediate compartment of taiep oligodendrocytes, a situation that could explain the hypomyelinated axons observed in this myelin mutant. The binding of microtubules to membranous organelles promotes the stabilization of microtubules, a feature that has important implications regarding its accumulation within the cytoplasm of oligodendrocytes during the temporal evolution of this neurologic disorder. The taiep rat is a myelin mutant with a long survival and could be a useful model for understanding dysmyelinating diseases in which the intracellular transport of myelin components is affected. J. Neurosci. Res. 47:573–581, 1997. © 1997 Wiley‐Liss, Inc.

Analysis of Chemokines and Receptors Expression Profile in the Myelin MutantTaiepRat

“…The mutation in the taiep rats that causes the microtubule accumulation in the oligodendrocyte and the consequent hypomyelination is still unknown [ 1 , 2 , 50 ]. Our results strongly suggest that the deficiency of the remyelination-stimulating factors such as CXCL1 and CXCR4 contributes to the failure in the process of remyelination in a microenvironment of chronic inflammation in the taiep rats.…”

“…The taiep rats exhibit hypomyelination and suffer progressive demyelination resulting in a highly hypomyelinated central nervous system (CNS) as they reach adulthood [ 1 , 2 ]. This demyelinating process has been associated with nitrosative stress in vivo and in vitro [ 3 , 4 ], glial-microglial activation and lymphocyte migration [ 4 ], and an increase in lipoperoxidation, caspase-3 activation, and cell death in vivo [ 5 ].…”

Neurophysiology

“…(Holmgren et al 1989) characterized by abnormal myelination (dysmyelination) and subsequent demyelination of the CNS (Duncan et ai. 1992;Couve et al 1997), due to a microtubular defect in oligodendrocytes (OLs). The optic nerve, myelinated by OLs, provides a suitable model of the CNS tract.…”

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

“…It was obtained at the Institute of Physiology of the Beneme ´rita Universidad Auto ´noma de Puebla, Me ´xico, as a spontaneous recessive tubulin mutation during the inbreeding process to obtain a subline of Sprague-Dawley with highyawning frequency [3,4]. The genetic change causes an initial hypomyelination followed by a progressive demyelination exclusively in the central nervous system (CNS) with a somatic recessive inheritance [3,5,6]. Recently, our research group demonstrated that taiep rats have a point mutation in Tubb4a gen and its corresponding protein TUBB4A (OMIM 602662), with pathological characteristics similar to the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC); [7,8].…”