HPA and Immune Axes in Stress: Involvement of the Serotonergic System
Pharmacology Department, National University of Ireland, Galway, Ireland. NeuroImmunoModulation
(Impact Factor: 1.88).
02/2006; 13(5-6):268-76. DOI: 10.1159/000104854
Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis and the immune system, acts as a trigger for anxiety and depression. There is experimental and clinical evidence that the rise in the concentration of pro-inflammatory cytokines and glucocorticoids, which occurs in a chronically stressful situation and also in depression, contributes to the behavioural changes associated with depression. A defect in serotonergic function is associated with these hormonal and immune changes. Neurodegenerative changes in the hippocampus, prefrontal cortex and amygdalae are the frequent outcomes of the changes in the hypothalamic-pituitary-adrenal axis and the immune system. Such changes may provide evidence for the link between chronic depression and dementia in later life.
Available from: Tania Di Raimo
- "Our finding is in agreement with previous results detecting increased levels of IL-18 in the brain of an autism experimental mouse model consisting of an inbred strain with behavioral deficits similar to those found in children with autism. In addition, IL-18 can enhance the production of toxic inflammatory molecules such as interferon (IFN)-γ and IL-1β[45,46], and recent experimental and clinical studies have proven the close connection between the rise of pro-inflammatory cytokines, glucocorticoids, and behavioral changes, such as those associated with anxiety and depression[47,48]. In this connection, the proinflammatory cytokines induce an altered serotonergic function by increasing the conversion of tryptophan to kynurenine. "
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ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disease which affects 1 in 88 children. Its etiology remains basically unknown, but it is apparent that neuroinflammation is involved in disease development. Great attention has been focused on pro-inflammatory cytokines, and several studies have reported their dysfunction unbalance in serum as well as in the brain. The present work aimed at evaluating putative dysregulation of interleukin-18 (IL-18), a pro-inflammatory cytokine of the IL-1 family in the sera of patients with ASD of different grades, compared to healthy controls, as well as in postmortem brain samples obtained from patients with tuberous sclerosis as well as acute inflammatory diseases. Moreover, quantitative analysis of IL-18 was performed in the sera and brain obtained from Reeler mice, an experimental model of autism.
Serum IL-18 levels were measured by ELISA. IL-18 was localized by immunohistochemical analysis in brain sections obtained from tuberous sclerosis and encephalitis patients, as well as from gender- and age-matched controls, and in the brain sections of both Reeler and wild-type mice. IL-18 was also quantified by Western blots in homogenates of Reeler and wild-type mice brains. IL-18 binding protein (IL-18BP) was evaluated in Reeler and wild-type mice plasma as well as in their brains (sections and homogenates).
IL-18 content decreased in the sera of patients with autism compared to healthy subjects and in Reeler sera compared to wild-type controls. IL-18 was detected within glial cells and neurons in the brain of subjects affected by tuberous sclerosis and encephalitis whereas in healthy subjects, only a weak IL-18 positivity was detected at the level of glial cells. Western blot identified higher amounts of IL-18 in Reeler brain homogenates compared to wild-type littermates. IL-18BP was expressed in higher amounts in Reeler brain compared to the brain of wild-type mice, whereas no significant difference was detected comparing IL-18BP plasma levels.
IL-18 is dysregulated in ASD patients. Further studies seemed necessary to clarify the molecular details behind IL-18 increase in the brain and IL-18 decrease in the sera of patients. An increase in the size of the patient cohort seems necessary to ascertain whether decreased IL-18 content in the sera can become a predictive biomarker of ASD and whether its measure, in combination with other markers (e.g., increased levels of brain-derived neurotrophic factor (BDNF)), may be included in a diagnostic panel.
Available from: journals.uio.no
- "This is of interest in light of that the HPA axis is complexly interconnceted with many of these neurosystems, e.g. monoaminergic and glutamatergic (Leonard, 2005; Meijer & de Kloet, 1998; Muller & Schwarz, 2007), and that the understanding of this network is likely to require a more detailed disection of the variabilities in these genes, as well as a consideration of interacting or redundant effects between genes, in the context of environmental stress (Kendler, 2005). Thus, the exploration of the HPA axis at the level of genetic variability hold promises of delivering significant explanations as to why certain individuals are at risk for suicidality, in connection to MD or other conditions of stress, as well as being seemingly necessary for the construction of reliable diagnostic and treatment tools, with sufficient sensitivity and specificity for the suicidal aspect of these patients. "
- "At the cortical level, evidence suggests that yoga helps in pain reduction due to production of endorphin resulting from alternate stretch and relax procedures of physical postures done with awareness. At limbic level, yoga offers mastery over the emotional surges through controlled and need based physiological responses to stressfully demanding situations instead of uncontrolled overtones of (HPA axis) hypothalamo-pituitary-adrenal axis during chronic pain. Studies also point to reduction in sympathetic arousal following yoga based relaxation techniques. "
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ABSTRACT: Background:Studies have shown that Integrated Yoga reduces pain, disability, anxiety and depression and increases spinal flexibility and quality-of-life in chronic low back pain (CLBP) patients.Objective:The objective of this study was to compare the effect of two yoga practices namely laghu shankha prakshalana (LSP) kriya, a yogic colon cleansing technique and back pain specific asanas (Back pain special technique [BST]) on pain, disability, spinal flexibility and state anxiety in patients with CLBP.Materials and Methods:In this randomized control (self as control) study, 40 in-patients (25 were males, 15 were females) between 25 and 70 years (44.05 ± 13.27) with CLBP were randomly assigned to receive LSP or BST sessions. The measurements were taken immediately before and after each session of either of the practices (30 min) in the same participant. Randomization was used to decide the day of the session (3rd or 5th day after admission) to ensure random distribution of the hang over effect of the two practices. Statistical analysis was performed using the repeated measures analysis of variance.Results:Significant group * time interaction (P < 0.001) was observed in 11 point numerical rating scale, spinal flexibility (on Leighton type Goniometer) and (straight leg raise test in both legs), Oswestry Disability Index, State Anxiety (XI component of Spieldberger's state and trait anxiety inventory. There was significantly (P < 0.001, between groups) better reduction in LSP than BST group on all variables. No adverse effects were reported by any participant.Conclusion:Clearing the bowel by yoga based colon cleansing technique (LSP) is safe and offers immediate analgesic effect with reduced disability, anxiety and improved spinal flexibility in patients with CLBP.
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