The effects of unilateral 6-hydroxydopamine (6-OHDA) treatment on striatal serotonin neurons in 12-day-old mice were studied using immunohistochemistry. The unilateral 6-OHDA lesions were evaluated with tyrosine hydroxylase (TH) immunohistochemistry. The majority of the TH-immunoreactive structures disappeared from the substantia nigra and neostriatum on the 6-OHDA lesioned side. However, the density of serotonin fibers was markedly increased throughout the 6-OHDA-depleted neostriatum 1 year later. These results suggest that serotonergic heterotypic sprouting may be permanent.
The effects of neonatal asphyxia on the serotonin neuron system were examined using the immunoperoxidase method. Male mice, 2 days of age, were exposed to total asphyxia (100% C02) for 30 min. Mice that spontaneously survived were perfused transcardially with a fixative at 15, 30 and 60 days of age. Quantitative immunohistochemical analysis at 60 days of age demonstrated a significant decrease in the numbers of serotonin-immunoreactive cell bodies in the nucleus raphe dorsalis, the nucleus raphe pontis, the sub-pyramidal region, the total raphe system and the whole brain, while no significant reduction in the number of serotonin-immunoreactive cell bodies was observed in the caudal raphe system. Presumably degenerative changes in serotonin-immunoreactive fibers were observed in various parts of the brain of mice subjected to total asphyxia at 15 days of age, and the numbers of degenerated fibers decreased in almost all parts of the brain, the exception being the caudal portion of the brainstem, at 30 and 60 days of age. These results suggested that neonatal asphyxia induced permanent changes in the serotonin neuron system, with regional differences.
We examined histochemical changes in Nissl's staining, glial fibrillary acidic protein (GFAP)-and myelin basic protein (MBP)-immunoreactive cell bodies and fibers in mouse brains after intraperitoneal or intraventricular injection of FK506 (tacrolimus, Prograf ® ). After intraperitoneal injection of FK506, there were no marked changes in either GFAP-and MBPimmunohistochemical staining or Nissl's staining. After intraventricular injection, there were no marked changes in either MBP-immunohistochemical staining or Nissl's staining, but extensive increases in GFAP-immunoreactive cell bodies and the densities of GFAP-immunoreactive fibers were detected in the olfactory tubercle, caudate putamen, hippocampus and neo-cortex. In this study, there were no statistically significant differences in GFAP-immunoreactive cell bodies, or the densities of GFAP-immunoreactive fibers between the FK506 injected group and placebo group. These results suggest that FK506 itself does not demonstrate neurotoxicity. However, various factors such as vasoconstriction appear under various conditions, such as GVHD or infection in vivo, especially after organ transplantation. Therefore, it can be said that not only FK506, but also various other factors are involved in neurotoxicity and FK506-related leukoencephalopathy.
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