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 typ e axonal dystrophy of the primary afferent neurons in the gracile trac t of the spinal cord was marked by severe gliosis characterized by the hypertrophy and proliferation of the fibrous astrocytes. Immunocytoch emical observation for substance P (SP) revealed that SP-positive cell s 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 acid ic protein (GFAP) indicated that a strong correspondence exists betwee n GFAP-positive networks and SP-positive grains, suggesting that SP wa s accumulated in the cytoplasm of astrocytes. The networks of SP-posit ive astrocytes spread all over the gracile tract and were densest at t he subpial membrane. Similar lesions and SP activity were detected alo ng the marginal zone of the lateral and ventral funiculi. Using an ele ctron microscope, in addition to SP-positive axonal terminals in the g racile nucleus, most SP-positive cells in the gracile tract were ident ified as reactive astrocytes whose processes surrounded myelinated and nonmyelinated axons, and extended their foot processes to the blood v essels. By in situ hybridization histochemistry of SP mRNA, we confirm ed the synthesis of SP in the astrocytes. Although the functional sign ificance of SP within astrocytes is not established here, these result s imply that the astrocytes may play a role as a gliotransmitter throu gh which the progress of axonal degeneration in the spinal cord was mo dified.