Learning abilities, NGF and BDNF brain levels in two lines of TNF-alpha transgenic mice, one characterized by neurological disorders, the other phenotypically normal

In this study we used two lines of transgenic mice overexpressing tumor nec rosis factor alpha (TNF-alpha) in the central nervous system (CNS), one cha racterized by reactive gliosis, inflammatory demyelination and neurological deficits (Tg6074) the other showing no neurological or phenotypical altera tions (TgK3) to investigate the effect of TNF-alpha on brain nerve growth f actor (NGF) and brain-derived neurotrophic factor (BDNF) levels and learnin g abilities. The results showed that the amount of NGF in the brain of Tg60 74 and TgK3 transgenic mice is low in the hippocampus and in the spinal cor d, increases in the hypothalamus of Tg6074 and showed no significant change s in the cortex. BDNF levels were low in the hippocampus and spinal cord of TgK3. BDNF increased in the hypothalamus of TgK3 and Tg6074 while in the c ortex, BDNF increased only in Tg6074 mice. Transgenic mice also had memory impairments as revealed by the Morris Water Maze test. These findings indic ate that TNF-alpha significantly influences BDNF and NGF synthesis, most pr obably in a dose-dependent manner. Learning abilities were also differently affected by overexpression of TNF-alpha, but were not associated with infl ammatory activity. The possible functional implications of our findings are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.