Pathological study of pseudohypertrophy of the inferior olivary nucleus

There have been only a few reports about the immunohistochemical study of pseudohypertrophy of the inferior olivary nucleus (PH-IO). We therefore performed the detailed immunohistochemical study of 10 PH-IOs in 8 patients to clarify the mechanism of neuronal degeneration and its related phenomenon of PH-IO. We used various antibodies to alphaB-crystallin (alphaBC), synaptophysin (SYP), microtubule-associated protein 2 (MAP2), Lys-Asp-Glu-Leu (KDEL) receptors, heat shock protein (HSP) 27 as well as SMI-31. We found alphaBC-positive neurons on the ipsilateral side of 10 PH-IOs. SMI-31-positive neurons were also observed in 6 PH-IOs. Confocal laser microscopy showed co-localization of alphaBC and SMI-31 in some neurons. However, there were no HSP27-positive neurons or astrocytes in any of the 10 PH-IOs. MAP2 immunostaining showed MAP2-positive hypertrophic thick neurites around hypertrophic neurons on the ipsilateral side of 7 PH-IOs and demonstrated "glomeruloid structures" in 3 PH-IOs. In addition, fine granular SYP-immunoreactivity was decreased in the neuropils on the ipsilateral side of all 10 PH-IOs. SYP-immunoreactive dots were scattered in the neuropils and on the neuronal cell bodies on the side of 7 PH-IOs, and the aggregation of SYP-immunoreactive dots scattered in the neuropils was shown in 3 PH-IOs. Double-immunostainings using anti-MAP2 and anti-SYP antibodies demonstrated frequent SYP-immunoreactive dots along the MAP2-positive hypertrophic thick neurites and their cell bodies. Periphery-stained KDEL-positive neurons were also found on the side of 7 PH-IOs. We showed that the change of the distribution of presynaptic terminals correlated well to the hypertrophic thick neurites in PH-IO. Our immuohistochemical stainings demonstrated various changes which occurred to the neurons in PH-IO, and their neurites and presynaptic terminals. We considered that alphaBC was expressed in the neurons in PH-IO, induced by cellular stress. Such a detailed immunohistochemical investigation has not been reported previously.