Behavioral characterization of mice lacking the neurite outgrowth inhibitor Nogo-A

Genes Brain Behav. 2009 Mar;8(2):181-92. doi: 10.1111/j.1601-183X.2008.00460.x. Epub 2008 Dec 3.

Abstract

The membrane protein Nogo-A inhibits neurite outgrowth and regeneration in the injured central nervous system, primarily because of its expression in oligodendrocytes. Hence, deletion of Nogo-A enhances regeneration following spinal cord injury. Yet, the effects of Nogo-A deletion on general behavior and cognition have not been explored. The possibility of potential novel functions of Nogo-A beyond growth inhibition is strongly suggested by the presence of subpopulations of neurons also expressing Nogo-A - not only during development but also in adulthood. We evaluated here Nogo-A(-/-) mice in a series of general basic behavioral assays as well as functional analyses related to brain regions with notable expression levels of Nogo-A. The SHIRPA protocol did not show any major basic behavioral changes in Nogo-A(-/-) mice. Anxiety-related behavior, pain sensitivity, startle reactivity, spatial learning, and associative learning also appeared indistinguishable between Nogo-A(-/-) and control Nogo-A(+/+) mice. However, motor co-ordination and balance were enhanced in Nogo-A(-/-) mice. Spontaneous locomotor activity was also elevated in Nogo-A(-/-) mice, but this was specifically observed in the dark (active) phase of the circadian cycle. Enhanced locomotor reaction to systemic amphetamine in Nogo-A(-/-) mice further pointed to an altered dopaminergic tone in these mice. The present study is the first behavioral characterization of mice lacking Nogo-A and provides significant insights into the potential behavioral relevance of Nogo-A in the modulation of dopaminergic and motor functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Anxiety / genetics
  • Anxiety / psychology
  • Association Learning / physiology
  • Avoidance Learning / physiology
  • Behavior, Animal / physiology*
  • Central Nervous System Stimulants / pharmacology
  • Cerebellum / cytology
  • Cerebellum / physiology
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Hypothalamus / cytology
  • Hypothalamus / physiology
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Myelin Proteins / genetics*
  • Neurons / physiology
  • Nogo Proteins
  • Pain Measurement
  • Postural Balance / physiology
  • Psychomotor Performance / physiology
  • Reflex, Startle / physiology
  • Retinal Ganglion Cells / physiology

Substances

  • Central Nervous System Stimulants
  • Myelin Proteins
  • Nogo Proteins
  • Rtn4 protein, mouse
  • Amphetamine