Learning performances, brain NGF distribution and NPY levels in transgenicmice expressing TNF-alpha

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in a variety of neurobiological activities including changing behavior and regulation o f both neurotrophin and neuropeptide levels. In this study we used two line s of transgenic mice overexpressing brain TNF-alpha characterized by neurol ogical deficits (line Tg6074) or phenotypically normal (line TgK3). We anal yzed whether or not impairments in learning and memory processes due to TNF -alpha overexpression were associated with changes in endogenous brain NGF, NPY and beta-amyloid. The results indicate that full TNF-alpha transgene e xpression disrupted the learning capabilities of transgenic mice (both Tg60 74 and TgK3). NGF decreased in the hippocampus of both transgenic mice wher eas hippocampal NPY slightly potentiated in Tg6074. The decrease in NGF is correlated with deficits in spatial learning and memory whereas inflammatio n in the brain of Tg6074 could be responsible of the hippocampal increase i n NPY. As a whole, these results show that transgenic mice overexpressing T NF-alpha in the brain represent a useful model for studying neuronal degene ration and brain inflammatory processes. (C) 2000 Elsevier Science B.V. All rights reserved.