First Author | Taniike M | Year | 2002 |
Journal | J Neurosci | Volume | 22 |
Issue | 12 | Pages | 4885-96 |
PubMed ID | 12077186 | Mgi Jnum | J:77531 |
Mgi Id | MGI:2181932 | Doi | 10.1523/JNEUROSCI.22-12-04885.2002 |
Citation | Taniike M, et al. (2002) Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model. J Neurosci 22(12):4885-96 |
abstractText | The genetic demyelinating mouse 'twitcher' is a model of the human globoid cell leukodystrophy, caused by galactosylceramidase (GALC) deficiency. Demyelination in the twitcher brain is secondary to apoptotic death of oligodendrocytes (OLs). Lipocalin-type prostaglandin (PG) D synthase (L-PGDS), a protein expressed in mature OLs, was progressively upregulated in twitcher OLs; whereas expression of OL-associated proteins such as carbonic anhydrase II, myelin basic protein, and myelin-associated glycoprotein was downregulated during demyelination in twitcher brains. The upregulation of L-PGDS was more remarkable in perineuronal OLs than in interfascicular OLs. A larger number of L-PGDS-positive OLs was found in selected fiber tracts of twitcher brains where fewer apoptotic cells were detected. The distribution of L-PGDS-positive OLs was inversely related to the severity of demyelination, as assessed by accumulation of scavenger macrophages. Mice doubly deficient for L-PGDS and GALC disclosed a large number of apoptotic neurons, which were never seen in twitcher brains, in addition to an increased number of apoptotic OLs. A linear positive correlation was observed between the population of L-PGDS-positive OLs in the twitcher brain and the ratio of apoptotic nuclei in the double mutant versus those in the twitcher, suggesting a dose-dependent effect of L-PGDS against apoptosis. These lines of evidence suggest that L-PGDS is an anti-apoptotic molecule protecting neurons and OLs from apoptosis in the twitcher mouse. This is a novel example of OL-neuronal interaction. |