BDNF and VEGF in the pathogenesis of stress-induced affective diseases: An insight from experimental studies

Abstract

Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder

“…BDNF protein and mRNA expression are down-regulated in postmortem hippocampus in MDD and suicide (Dwivedi et al, 2003; Duric et al, 2010). In addition, exposure to chronic stress or glucocorticoids decreases the expression of BDNF protein and mRNA in the rodent hippocampus (Duman and Aghajanian, 2012; Nowacka and Obuchowicz, 2013). Antidepressant-like effects of BDNF itself are well-documented, and they may involve direct effects of BDNF on astrocytes (Nowacka and Obuchowicz, 2013).…”

Molecular mechanisms in the regulation of adult neurogenesis during stress

“…Several studies have shown a decrease in VEGF levels in the hippocampus of rats in response to both chronic and acute stress, whereas other studies, including both rat and mouse studies, have found no change in the level of this growth factor 100 . The majority of studies report that VEGF increases cell proliferation through the activation of VEGF receptor 2 (also known as FLK1), which is expressed in neural progenitors and induces CREB signalling [101][102][103][104] .…”

Increased levels of vascular endothelial growth factor in patients with major depressive disorder: A meta-analysis

“…For example, VEGF has been proven to promote neurogenesis in the hippocampus (Fournier and Duman, 2012), provide neuroprotection (Feng et al, 2011), effect responses to stress (Nowacka and Obuchowicz, 2013), influence synaptic transmission (McCloskey et al, 2005), and protect neurons from oxidative stress (Hao and Rockwell, 2013). Furthermore, in one study conducted on a post-mortem brain of a patient with schizophrenia, the authors reported a significantly lower VEGF mRNA expression localized in the post-mortem dorsolateral prefrontal cortex (Fulzele and Pillai, 2009).…”