Neurobehavioral alterations in developing transgenic mice expressing TNF-alpha in the brain

Brain Behav Immun. 1996 Jun;10(2):126-38. doi: 10.1006/brbi.1996.0013.


During development, neuronal circuitry and memory formation are associated with the synthesis and release of several biological mediators, including cytokines. Among the numerous cytokines, the role of tumor necrosis factor-alpha (TNF-alpha) in neurobehavioral development is largely unknown. Thus, the recently generated transgenic mice expressing murine TNF-alpha in the brain represent a valid animal model for investigating the role of TNF-alpha in neurobehavioral processes. Using these mice, we showed that an overexpression of murine TNF-alpha increases grooming in the novel object investigation test, decreases rearing as a reaction to novel olfactory cues, and produces a retardation of passive avoidance acquisition while enhancing the thermal response in the hot-plate test, a task regulated by both peripheral and central mechanisms. The possibility that these effects are associated with endogenous changes in concentration of the NGF, known to be modulated by TNF-alpha, is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Behavior, Animal / physiology*
  • Body Weight
  • Brain / metabolism*
  • Demyelinating Diseases / etiology*
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / psychology
  • Exploratory Behavior / physiology
  • Female
  • Globins / genetics
  • Grooming / physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factors / physiology
  • Reaction Time
  • Recombinant Fusion Proteins / biosynthesis*
  • Transgenes
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*


  • Nerve Growth Factors
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Globins