Changes in proinflammatory cytokines and white matter in chronically stressed rats

Abstract

Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies.

White Matter Microstructure Underlies the Effects of Sleep Quality and Life Stress on Depression Symptomatology in Older Adults

“…that increased MD, AD, and RD in the body of the corpus callosum and inferior cerebellar peduncle were significantly correlated with current stress levels, which were also reported with the populations with high early life stress and post-traumatic stress disorders (Paul et al, 2008;O'Doherty et al, 2018). According to correlative fMRI and cytokine studies in both animals and humans (Yang et al, 2015;Benedetti et al, 2016;Sugimoto et al, 2018), these alterations might reflect elevated levels of proinflammatory cytokines, like interleukin-1α and β, tumor necrosis factor-α and interleukin-6. In summary, our correlation analyses propose that both high depression and stress levels are linked with low myelin preservation of the corpus callosum.…”

Neuroinflammation and Depression: Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation

“…Stress has been associated to the development of clinical depression, and evidence from preclinical studies suggests a role of microglia in depression and stress. Most curious, chronic stress has been known to promote microglial hyper-ramification and astroglial atrophy (Tynan et al, 2013 ), as well as lower immunoreactivity of myelin basic protein (MBP) and fewer mature oligodendrocytes (Yang et al, 2015 ) in the prefrontal cortex of rodents. Other molecules that are gaining attention in depressive pathophysiology are the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) involved in learning and memory, whose expression is decreased in depressed patients, and the vascular endothelial growth factor (VEGF), an angiogenic cytokine, with decreased mRNA levels in peripheral leukocytes of such individuals (Dwivedi, 2009 ).…”

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

“…Stress evokes multiple behavioral and physiological responses 1 , 2 , including neuroendocrine and immune deficits 3 – 7 , that may trigger common affective illnesses, such as anxiety, depression and post-traumatic stress disorder (PTSD) 8 – 11 . Widespread, debilitating and often treatment-resistant, these neuropsychiatric disorders represent an urgent unmet biomedical problem 12 – 14 , complicated by their multiple overlapping genetic and environmental determinants, and poor understanding of their mechanisms and risk factors 15 , 16 .…”