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

Luigi Aloe, Francesca Properzi, Lesley Probert, Katerina Akassoglou, George Kassiotis, Alessandra Micera, Marco Fiore

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we used two lines of transgenic mice overexpressing tumor necrosis factor alpha (TNF-α) in the central nervous system (CNS), one characterized by reactive gliosis, inflammatory demyelination and neurological deficits (Tg6074) the other showing no neurological or phenotypical alterations (TgK3) to investigate the effect of TNF-α on brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels and learning abilities. The results showed that the amount of NGF in the brain of Tg6074 and TgK3 transgenic mice is low in the hippocampus and in the spinal cord, increases in the hypothalamus of Tg6074 and showed no significant changes 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 cortex, BDNF increased only in Tg6074 mice. Transgenic mice also had memory impairments as revealed by the Morris Water Maze test. These findings indicate that TNF-α significantly influences BDNF and NGF synthesis, most probably in a dose-dependent manner. Learning abilities were also differently affected by overexpression of TNF-α, but were not associated with inflammatory activity. The possible functional implications of our findings are discussed.

Original languageEnglish
Pages (from-to)125-137
Number of pages13
JournalBrain Research
Volume840
Issue number1-2
DOIs
Publication statusPublished - Sep 4 1999

Keywords

  • Behavior
  • CNS inflammation
  • Cytokine
  • Demyelination
  • Inflammation
  • Learning
  • TNF-α
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

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