Effect of Chronic Inescapable Footshock and Antidepressant Treatment on BDNF/TrkB Levels in Rat Hippocampus

Abstract

Depression is a major health problem globally. Chronic stress arising out of life style or social factors may trigger depression, the molecular basis of which has been attributed to alterations of brain chemicals like neurotrophins. Among these neurotrophins, brain-derived neurotrophic factor regulates many physiological functions in the brain, alteration of which has been well associated with the pathogenesis of depression. Stress-induced helplessness in rodents constitutes a well-defined model to investigate neurobiological mechanism of depression. In the present investigation, using this model, we investigated the correlation between stress-induced helplessness and BDNF, its receptor TrkB with two of its principal downstream signaling molecules ERK1,2 and Akt. BDNF level was measured by sandwich ELISA and its cognate receptor TrkB, together with downstream molecules ERK1,2 and Akt, was assayed by western blot. Chronic stressed rats exhibited down regulation of BDNF and TrkB along with ERK1,2 and Akt. This parallels the decreased escape behavior. The antidepressant drug Fluxetine hydrochloride (FLX)-treated rats exhibited significant increase in escape behavior in stress-induced helplessness which is correlated with restoration of BDNF, its receptor TrkB and expression of its downstream signaling molecules ERK1,2 and Akt. This supports the notion that pharmacological restoration of BDNF and its receptor TrkB may be of therapeutic value for depression.