Inflammation, depression and dementia: are they connected?
ABSTRACT Chronic inflammation is now considered to be central to the pathogenesis not only of such medical disorders as cardiovascular disease, multiple sclerosis, diabetes and cancer but also of major depression. If chronic inflammatory changes are a common feature of depression, this could predispose depressed patients to neurodegenerative changes in later life. Indeed there is now clinical evidence that depression is a common antecedent of Alzheimer's disease and may be an early manifestation of dementia before the cognitive declines becomes apparent. This review summarises the evidence that links chronic low grade inflammation with changes in brain structure that could precipitate neurodegenerative changes associated with Alzheimer's disease and other dementias. For example, neuronal loss is a common feature of major depression and dementia. It is hypothesised that the progress from depression to dementia could result from the activation of macrophages in the blood, and microglia in the brain, that release pro-inflammatory cytokines. Such cytokines stimulate a cascade of inflammatory changes (such as an increase in prostaglandin E2, nitric oxide in addition to more pro-inflammatory cytokines) and a hypersecretion of cortisol. The latter steroid inhibits protein synthesis thereby reducing the synthesis of neurotrophic factors and preventing reairto damages neuronal networks. In addition, neurotoxic end products of the tryptophan-kynurenine pathway, such as quinolinic acid, accumulate in astrocytes and neurons in both depression and dementia. Thus increased neurodegeneration, reduced neuroprotection and neuronal repair are common pathological features of major depression and dementia. Such changes may help to explain why major depression is a frequent prelude to dementia in later life.
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ABSTRACT: Depression is very common throughout the course of veterans' lives, and dementia is common in late life. Previous studies suggest an association between depression and dementia in military veterans. The most likely biologic mechanisms that may link depression and dementia among military veterans include vascular disease, changes in glucocorticoid steroids and hippocampal atrophy, deposition of β-amyloid plaques, inflammatory changes, and alterations of nerve growth factors. In addition, military veterans often have depression comorbid with posttraumatic stress disorder or traumatic brain injury. Therefore, in military veterans, these hypothesized biologic pathways going from depression to dementia are more than likely influenced by trauma-related processes. Treatment strategies for depression, posttraumatic stress disorder, or traumatic brain injury could alter these pathways and as a result decrease the risk for dementia. Given the projected increase of dementia, as well as the projected increase in the older segment of the veteran population, in the future, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize the principal mechanisms of this relationship and discuss treatment implications in military veterans.Alzheimer's and Dementia 06/2014; 10(3):S166–S173. DOI:10.1016/j.jalz.2014.04.007 · 17.47 Impact Factor
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ABSTRACT: Background: The prevalence of obesity is increasing rapidly and, has largely beenThe Medical journal of Cairo University 09/2013; 81(2):59.
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ABSTRACT: Both basic and clinical research indicates that females are more susceptible to stress-related affective disorders than males. One of the mechanisms by which stress induces depression is via inflammatory signaling in the brain. Stress during adolescence, in particular, can also disrupt the activation and continued development of both the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes, both of which modulate inflammatory pathways and brain regions involved in affective behavior. Therefore, we tested the hypothesis that adolescent stress differentially alters brain inflammatory mechanisms associated with affective-like behavior into adulthood based on sex. Male and female Wistar rats underwent mixed-modality stress during adolescence (PND 37-48) and were challenged with lipopolysaccharide (LPS; 250 μg/kg, i.p.) or saline 4.5 weeks later (in adulthood). Hippocampal inflammatory marker gene expression and circulating HPA and HPG axis hormone concentrations were then determined. Despite previous studies indicating that adolescent stress induces affective-like behaviors in female rats only, this study demonstrated that adolescent stress increased hippocampal inflammatory responses to LPS in males only, suggesting that differences in neuroinflammatory signaling do not drive the divergent affective-like behaviors. The sex differences in inflammatory markers were not associated with differences in corticosterone. In females that experienced adolescent stress, LPS increased circulating estradiol. Estradiol positively correlated with hippocampal microglial gene expression in control female rats, whereas adolescent stress negated this relationship. Thus, estradiol in females may potentially protect against stress-induced increases in neuroinflammation.Brain Behavior and Immunity 01/2013; 26. DOI:10.1016/j.bbi.2013.01.075 · 6.13 Impact Factor