Limits...
A role for hemopexin in oligodendrocyte differentiation and myelin formation.

Morello N, Bianchi FT, Marmiroli P, Tonoli E, Rodriguez Menendez V, Silengo L, Cavaletti G, Vercelli A, Altruda F, Tolosano E - PLoS ONE (2011)

Bottom Line: In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx- mice were strongly reduced starting at 2 months and progressively decreased with age.Finally, in vitro experiments showed that Hx promotes OL differentiation.Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biotechnology Center, University of Turin, Turin, Italy.

ABSTRACT
Myelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which is also locally produced in the CNS by ependymal cells, neurons and glial cells. We have recently reported that oligodendrocytes (OLs) are the type of cells in the brain that are most susceptible to lack of Hx, as the number of iron-overloaded OLs increases in Hx- brain, leading to oxidative tissue damage. In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx- mice were strongly reduced starting at 2 months and progressively decreased with age. Myelin abnormalities were confirmed by electron microscopy and, at the functional level, resulted in the inability of Hx- mice to perform efficiently on the Rotarod. It is likely that the poor myelination in the brain of Hx- mice was a consequence of defective maturation of OLs as we demonstrated that the number of mature OLs was significantly reduced in mutant mice whereas that of precursor cells was normal. Finally, in vitro experiments showed that Hx promotes OL differentiation. Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.

Show MeSH

Related in: MedlinePlus

Motor dysfunction in Hx−/− mice.Accelerated Rotarod tests were performed every fifteen days from two to                            twelve months of age. The mean time score in which the mice walked in                            synchrony with the rod was recorded. Each test consisted of three                            consecutive trials. Hx−/− mice showed significant                            motor impairment starting from four months of age and increasing with                            age. Data represent mean ± SEM, n = 16 mice                            for each genotype. * =  P<0.05, **                             = P<0.01, ***                             = P<0.001.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3102107&req=5

pone-0020173-g004: Motor dysfunction in Hx−/− mice.Accelerated Rotarod tests were performed every fifteen days from two to twelve months of age. The mean time score in which the mice walked in synchrony with the rod was recorded. Each test consisted of three consecutive trials. Hx−/− mice showed significant motor impairment starting from four months of age and increasing with age. Data represent mean ± SEM, n = 16 mice for each genotype. * =  P<0.05, **  = P<0.01, ***  = P<0.001.

Mentions: To assess whether hypomyelination in motor cortex of Hx−/− mice had an effect on motor function, we tested motor coordination ability in these animals from 2 to 12 months of age, using the Rotarod test (Figure 4). The performance of wild-type mice was unchanged with increasing age, whereas in the Hx−/− mice motor coordination deteriorated progressively by 4 months of age. The reduction in motor function in Hx−/− mice became significant by seven months of age (mean score reduction of 23%) and worsened gradually until twelve months of age (mean score reduction of 34%).


A role for hemopexin in oligodendrocyte differentiation and myelin formation.

Morello N, Bianchi FT, Marmiroli P, Tonoli E, Rodriguez Menendez V, Silengo L, Cavaletti G, Vercelli A, Altruda F, Tolosano E - PLoS ONE (2011)

Motor dysfunction in Hx−/− mice.Accelerated Rotarod tests were performed every fifteen days from two to                            twelve months of age. The mean time score in which the mice walked in                            synchrony with the rod was recorded. Each test consisted of three                            consecutive trials. Hx−/− mice showed significant                            motor impairment starting from four months of age and increasing with                            age. Data represent mean ± SEM, n = 16 mice                            for each genotype. * =  P<0.05, **                             = P<0.01, ***                             = P<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102107&req=5

pone-0020173-g004: Motor dysfunction in Hx−/− mice.Accelerated Rotarod tests were performed every fifteen days from two to twelve months of age. The mean time score in which the mice walked in synchrony with the rod was recorded. Each test consisted of three consecutive trials. Hx−/− mice showed significant motor impairment starting from four months of age and increasing with age. Data represent mean ± SEM, n = 16 mice for each genotype. * =  P<0.05, **  = P<0.01, ***  = P<0.001.
Mentions: To assess whether hypomyelination in motor cortex of Hx−/− mice had an effect on motor function, we tested motor coordination ability in these animals from 2 to 12 months of age, using the Rotarod test (Figure 4). The performance of wild-type mice was unchanged with increasing age, whereas in the Hx−/− mice motor coordination deteriorated progressively by 4 months of age. The reduction in motor function in Hx−/− mice became significant by seven months of age (mean score reduction of 23%) and worsened gradually until twelve months of age (mean score reduction of 34%).

Bottom Line: In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx- mice were strongly reduced starting at 2 months and progressively decreased with age.Finally, in vitro experiments showed that Hx promotes OL differentiation.Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biotechnology Center, University of Turin, Turin, Italy.

ABSTRACT
Myelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which is also locally produced in the CNS by ependymal cells, neurons and glial cells. We have recently reported that oligodendrocytes (OLs) are the type of cells in the brain that are most susceptible to lack of Hx, as the number of iron-overloaded OLs increases in Hx- brain, leading to oxidative tissue damage. In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx- mice were strongly reduced starting at 2 months and progressively decreased with age. Myelin abnormalities were confirmed by electron microscopy and, at the functional level, resulted in the inability of Hx- mice to perform efficiently on the Rotarod. It is likely that the poor myelination in the brain of Hx- mice was a consequence of defective maturation of OLs as we demonstrated that the number of mature OLs was significantly reduced in mutant mice whereas that of precursor cells was normal. Finally, in vitro experiments showed that Hx promotes OL differentiation. Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.

Show MeSH
Related in: MedlinePlus