2004]. Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Recently, the involvement of neurotrophic factors, particularly brain-derived

neurotrophic factor (BDNF), have been under intense investigation regarding their possible role in the pathophysiology of mood disorders and its antidepressant effects [Castren et al. 2007]. BDNF is a small dimeric neuroprotective protein and a member of the neurotrophin family, which is widely expressed in the mammalian adult brain [Hofer et al. 1990]. Its normal physiological role is to encourage the outgrowth of dendrites from nerve endings, and to help stabilize Inhibitors,research,lifescience,medical connections between neurons [Hartmann et al. 2001]. Inhibitors,research,lifescience,medical According to the neurotrophin hypothesis of depression, BDNF is of major importance because it modulates the plasticity, inhibits cell death cascades and increases cell survival proteins that are responsible for the proliferation and maintenance of central nervous system neurons [Yulug et al. 2009]. Some animal models of depression showed that both Inhibitors,research,lifescience,medical acute and chronic stress decreased expression of BDNF [Angelucci et al. 2000; Roceri et al. 2002], and direct administration of BDNF into specific brain regions has been shown to mimic antidepressant effects [Siuciak et al. 1997; Hoshaw et al. 2005; Shirayama et al. 2002]. However, some authors reported that mutant mouse lines

with low or no detectable BDNF expression did not exhibit depressive-like behaviour [Chan et al. 2006; Chourbaji et al. 2004; MacQueen et al. 2001; Saarelainen et al. 2003]. Pan and colleagues demonstrated that BDNF crosses the blood–brain barrier (BBB), which suggests

that serum BDNF levels may reflect BDNF levels of the brain [Pan et al. 1998]. It was found that brain and serum Inhibitors,research,lifescience,medical BDNF levels undergo similar changes during maturation and ageing, and there is a positive correlation between Inhibitors,research,lifescience,medical serum and cortical BDNF levels [Karege et al. 2002]. Data about serum BDNF MG-132 mouse concentrations in major depression are conflicting, some authors reported levels as decreased [Karege et al. 2002, 2005; Shimizu et al. 2003; Aydemir et al. 2006; Monteleone et al. 2008], and others as unchanged [Ziegenhorn et al. 2007], compared with the healthy controls. Serum levels of BDNF have been found to be 200-fold higher than Carnitine dehydrogenase plasma levels [Rosenfeld et al. 1995]. This difference could reflect the amount of BDNF stored in platelets. Accordingly, it was suggested that BDNF levels of the plasma may reflect circulating levels since platelets are not seriously damaged during the separation of plasma [Lee et al. 2007]. However, studies that investigated plasma BDNF levels of depressed patients also yielded conflicting results as decreased, unchanged or increased levels [Grassi-Oliveira et al. 2008; Karege et al. 2005; Lee et al. 2007; Piccinni et al. 2008; Lee and Kim, 2009; Bocchio-Chiavetto et al. 2010; Serra-Millàs et al. 2011].