Role of NGF/TrkA signaling milieu in depressogenic induction of rat brain

Objectives: Stress-induced helplessness in rodents constitutes a well-defined model to investigate neurobiological mechanism of depression. In the present investigation, we investigated the correlation between stress induced helplessness and NGF, its receptor TrkA with two of its principal downstream signaling molecule ERK1, 2 and Akt. Background: Nerve Growth factor (NGF) regulates many physiological functions in the brain, alteration of which has been well associated with the pathogenesis of depression. Method: NGF level was measured by Sandwich ELISA and its cognate receptor TrkA and downstream molecules ERK 1, 2, Akt were assayed by Western blot. Result: Chronic stressed rats exhibited down regulation of NGF and TrkA along with ERK1, 2 and Akt. This parallels with the decreased escape behavior. The antidepressant drug Fluoxetine hydrochloride (FLX) treated rats exhibited significant increase in escape deficit in stress induced Learned helplessness. This was correlated with the restoration of NGF levels, its cognate receptor TrkA and expression of its down stream signaling molecules ERK1, 2 and Akt in hippocampus of rat brain. Conclusion: This supports the notion that pharmacological restoration of NGF and its receptor TrkA may be of therapeutic value for the treatment of depression.