Selective Nuclear Shrinkage of Oligodendrocytes Lacking Glial Cytoplasmic Inclusions in Multiple System Atrophy: A 3-Dimensional Volumetric Study

Glial cytoplasmic inclusions (GCIs) are a pathologic hallmark of multiple system atrophy (MSA), but their pathogenetic roles need to be clarified. To determine possible roles of GCIs in individual cells, serial optical sections obtained by confocal microscopy were reconstructed to yield 3-dimensional (3D) images of the nuclei to quantify nuclear volume. Oligodendroglial nuclear volumes were determined in the pons of 6 MSA and 7 control patients. The nuclear volumes were significantly smaller in the MSA group as a whole (135.81 +/- 60.83 mu m(3), mean +/- SD; n = 404) than in the control group (188.05 +/- 55.71 mu m(3); n = 308; p < 0.001). This difference was due to a significantly smaller nuclear volume of oligodendrocytes without GCIs (GCI(-) group, 91.26 +/- 23.77 mu m(3); n = 210) compared with the control group (p < 0.001) and compared with the oligodendrocytes with GCIs (GCI(+) group, 184.03 +/- 51.18 mu m(3); n = 194; p < 0.001); the difference between the latter GCI(+) and control groups was not significant (p > 0.05). This selective decrease in nuclear volume restricted to the GCI(-) group cannot be explained if nuclear shrinkage was accelerated in the presence of GCIs. Conversely, GCI formation might be linked, either directly or indirectly, to a mechanism that counteracts rather than accelerates nuclear shrinkage. This novel 3-dimensional strategy provides pivotal data that link GCI formation and degeneration in MSA.