Substance P-immunoreactive astrocytes in gracile sensory nervous tract of spinal cord in gracile axonal dystrophy mutant mouse.

In the gracile axonal dystrophy (GAD) mutant mouse, the dying-back type axonal dystrophy of the primary afferent neurons in the gracile tract of the spinal cord was marked by severe gliosis characterized by the hypertrophy and proliferation of the fibrous astrocytes. Immunocytochemical observation for substance P (SP) revealed that SP-positive cells increased in the lesioned sites, primarily in the gracile nucleus of the medulla and subsequently in the gracile fasciculus of the spinal cord. The combined immunostaining of both SP and glial fibrillary acidic protein (GFAP) indicated that a strong correspondence exists between GFAP-positive networks and SP-positive grains, suggesting that SP was accumulated in the cytoplasm of astrocytes. The networks of SP-positive astrocytes spread all over the gracile tract and were densest at the subpial membrane. Similar lesions and SP activity were detected along the marginal zone of the lateral and ventral funiculi. Using an electron microscope, in addition to SP-positive axonal terminals in the gracile nucleus, most SP-positive cells in the gracile tract were identified as reactive astrocytes whose processes surrounded myelinated and nonmyelinated axons, and extended their foot processes to the blood vessels. By in situ hybridization histochemistry of SP mRNA, we confirmed the synthesis of SP in the astrocytes. Although the functional significance of SP within astrocytes is not established here, these results imply that the astrocytes may play a role as a gliotransmitter through which the progress of axonal degeneration in the spinal cord was modified.