ASE-DEPENDENT SUSCEPTIBILITY OF CNS GLIAL POPULATIONS IN-SITU TO THE ANTIMETABOLITE 6-AMINONICOTINAMIDE

Intraperitoneal injections of the nicotinamide antagonist 6-aminonicot inamide (6-AN) were used to determine if there are regional difference s in putative glial energy metabolism between the developing and adult rat CNS. 6-AN shuts down the hexose monophosphate pathway, which is u sed preferentially by astrocytes and oligodendrocytes. These cells sub sequently undergo cytotoxic edema and cell death. Adult rats and pups ranging in age from 7 to 31 d received a single injection of 6-AN and were sacrificed after 24 h. As demonstrated with immunocytochemical st aining for the astroglia-specific markers GFAP and S-100 beta, the 7-9 -d-old animals exhibited a uniform appearance with edematous glial cel ls located throughout the CNS. However, with advancing age, a consiste nt pattern of progressively decreasing amounts of injured glia, which has not been previously described, occurred in cerebral and cerebellar structures. After 3 wk postnatal, the adult pattern was manifested in which glial degeneration occurred only in specific regions of the spi nal cord, cerebellum, medulla, and thalamus, whereas the remainder of the CNS appeared normal. The results suggest the presence of heterogen eous populations of glia whose preferred use of the hexose monophospha te pathway is predicated on both the age of the animal and their locat ion in the CNS.