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Resilience factor low in depression, protects mice from stress

ibility or resilience to developing the depression-like behaviors. It counteracted the strong tendency to learn an association, or generalize, the aversive experience to all mice.
  • Induction of deltaFosB was required for the antidepressant fluoxetine (Prozac) to reverse the stress-induced depression-like syndrome.
  • Prolonged isolation from environmental stimuli reduced levels of deltaFosB, increasing vulnerability to depression-like behaviors.
  • Among numerous target genes regulated by deltaFosB, a gene that makes a protein called the AMPA receptor is critical for resilience or protecting mice from the depression-like syndrome. The AMPA receptor is a protein on neurons that boosts the cell's activity when it binds to the chemical messenger glutamate.
  • Increased activity of neurons triggered by heightened sensitivity of AMPA receptors to glutamate increased susceptibility to stress-induced depression-like behavior.
  • Induction of deltaFosB calmed the neurons and protected against depression by suppressing AMPA receptors' sensitivity to glutamate.
  • Post-mortem brain tissue of depressed patients contained only about half as much deltaFosB as that of controls, suggesting that poor response to antidepressant treatment may be traceable, in part, to weak induction of the transcription factor.

    Reduced deltaFosB in the reward hub likely helps to account for the impaired motivation and reward behavior seen in depression, said Nestler. Boosting it appears to enable an individual to pursue goal-directed behavior despite stress.

    The high-tech screening for molecules that boost DeltaFosB, supported by the Recovery Act grant, could lead to development of medications that would help people cope with chronic stress. The molecules could also potentially be used as telltale tracers in brain imaging to chart depressed patients' treatment progress by reflecting changes in deltaFosB, said Nestler.


  • Contact: Jules Asher
    NIH/National Institute of Mental Health

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