Heterogeneity between hippocampal and septal astroglia as a contributing factor to differential in vivo AMPA excitotoxicity.

Abstract

Astroglial participation in the regional differences of vulnerability to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced neurodegeneration was investigated in the rat hippocampus and medial septum using L-alpha-aminoadipate (alpha-AA) as a specific astroglial toxin. alpha-AA was microinjected in the hippocampus and the medial septum and a time-course study was carried out between 2 hr and 3 days. When compared to controls, microinjection of alpha-AA in the hippocampus induced within 3 days a reversible loss of glial fibrillary acidic protein (GFAP) immunostaining and a microglial reaction without any neuronal loss, whereas in the medial septum it caused no effects on astroglial, microglial, or neuronal populations. Differences in hippocampus and medial septum vulnerability were also evidenced when alpha-AA was co-injected with AMPA and neurodegeneration was assessed in terms of neuronal loss, glial reactions, calcification, and atrophy of the area. In the hippocampus, alpha-AA increased AMPA excitotoxicity with marked disorganization of all hippocampal subfields, increased neuronal loss, a more important astroglial reaction, a larger area of microgliosis, and a greater abundance of calcium deposits. By contrast, in the medial septum alpha-AA did not modify any parameter of the AMPA-induced lesion. In conclusion, the presence of different astroglial populations in hippocampus and medial septum results in a different participation to AMPA excitotoxicity that may determine, at least in part, the specific regional vulnerability to neurodegeneration.