Developmental changes in the cellular distribution of glutathione and glutathione S-transferases in the murine nervous system.

The distribution of glutathione (GSH) and glutathione S-transferases (GSTs) in the adult rat brain is cell-type specific, but their cellular distribution in the developing central nervous system is unknown. In the present study, GSH distribution in the mouse nervous system was visualized by mercury orange histochemistry and class-specific GSTs were localized by immunohistochemistry at ages E13 to PN30. Both neuronal and glial progenitor cells stain uniformly positive for GSH at E13. Spinal anterior horn neurons become GSH-negative by E17, at which time neurons and glia in other CNS regions are still GSH-positive. By PN5, most neurons have lost GSH staining and are surrounded by GSH-rich neuropil, ependyma, and vasculature. Olfactory mitral and granule cells, cerebellar granule cells, and dorsal root ganglion (DRG) neurons retain consistently high levels of GSH throughout development and into adulthood. Immunoreactivity to alpha-class GST antisera is not observed in the CNS until PN10, when very weak staining becomes apparent in the pia, ependyma, choroid plexus and neurons throughout the brain and spinal cord. Immunoreactivity to mu-GST is observed in neurons and astrocytes (but not oligodendrocytes), pia, ependyma, and choroid plexus throughout the brain by PN10. pi-GST immunoreactivity is observed in all cells of the embryonic nervous system. Postnatally, it is found in neurons and oligodendrocytes (but not astrocytes) in all regions of the brain and spinal cord as well as in pia, ependyma, and choroid plexus. The neurons and satellite cells of the DRG are immunoreactive to alpha-, mu-, and pi-GST antisera at all time points examined. The developmental changes in the cellular distribution of GSH and GSTs suggest that enzymatic conjugation and antioxidant activities may also be cell specific during brain development.

3-Acetylpyridine-induced degeneration in the dorsal root ganglia: involvement of small diameter neurons and influence of axotomy.

3-Acetylpyridine (3-AP), an analogue of nicotinamide, produces highly selective CNS lesions, the severity of which may be influenced by prior alterations in the metabolic activity of the affected neurons. The present study was undertaken to determine whether prior axotomy modified the response of dorsal root ganglia (DRG) and anterior horn (AH) neurons to 3-AP. A single administration (50 or 80 mg/kg i.p.) of 3-AP to adult rats resulted in degeneration of primarily small-dark DRG neurons by 24 h. The AH neurons were not affected by either dose of 3-AP. Light and electron microscopy of the DRG revealed a spectrum of damage ranging from loss of Nissl substance and cytoplasmic degradation to frank necrosis with neuronophagia. Frequently, injured neurons exhibited perinuclear aggregation of cytoplasmic organelles with dissolution of Nissl substance, clearing of the peripheral cytoplasm, and formation of large peripheral vacuoles. Occasionally, a second pattern of 3-AP injury was observed in which the nuclear chromatin of the neurons was condensed and there was formation of small vacuoles throughout the cytoplasm without peripheral clearing or perinuclear aggregation of cytoplasmic organelles. Axotomy induced typical axon reactions in both large-pale and small-dark DRG neurons. The combination of axotomy followed by 3-AP 4 days later produced morphological features characteristic of both axotomy and 3-AP exposure, but did not appear to alter the incidence of neuronal cell death. The almost exclusive vulnerability of the small dorsal root ganglion neurons to 3-AP neurotoxicity make this model potentially useful for the study of small fibre neuropathies.