Brain, behavior, and immunity
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Brain Behav. Immun. · Jan 2010
Glial cell line-derived neurotrophic factor acutely modulates the excitability of rat small-diameter trigeminal ganglion neurons innervating facial skin.
Glial cell line-derived neurotrophic factor (GDNF) plays an important role in adult sensory neuron function. However, the acute effects of GDNF on primary sensory neuron excitability remain to be elucidated. The aim of the present study was to investigate whether GDNF acutely modulates the excitability of adult rat trigeminal ganglion (TRG) neurons that innervate the facial skin by using perforated-patch clamping, retrograde-labeling and immunohistochemistry techniques. ⋯ GDNF application also increased the duration of the repolarization phase and decreased the duration of the depolarization phase of the action potential, and these characteristic effects were also abolished by co-application of K252b. These results suggest that acute application of GDNF enhances the neuronal excitability of adult rat small-diameter TRG neurons innervating the facial skin, via activation of GDNF-induced intracellular signaling pathway. We therefore conclude that a local release of GDNF from TRG neuronal soma and/or nerve terminals may regulate normal sensory function, including nociception.
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Brain Behav. Immun. · Jan 2010
Regulation of cytokine signaling and T-cell recruitment in the aging mouse brain in response to central inflammatory challenge.
Aging is often accompanied by increased levels of inflammatory molecules in the organism, but age-related changes in the brain response to inflammatory challenges still require clarification. We here investigated in mice whether cytokine signaling and T-cell neuroinvasion undergo age-related changes. We first analyzed the expression of molecules involved in T-cell infiltration and cytokine signaling regulation in the septum and hippocampus of 2-3 months and 20- to 24-month-old mice at 4h after intracerebroventricular injections of tumor necrosis factor (TNF)-alpha or interferon-gammaversus saline injections. ⋯ CD3(+), CD4(+) and CD8(+) T-cells exhibited progressive age-related increases in brain parenchyma and choroid plexus after cytokine exposure. The findings indicate that the brain responses to inflammatory challenges are not only preserved with advancing age, but also include gradual amplification of ICAM-1 expression and T-cell recruitment. The data highlight molecular and cellular correlates of age-related increase of brain sensitivity to inflammatory stimuli, which could be involved in altered brain vulnerability during aging.
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Brain Behav. Immun. · Oct 2009
Decreased neuronal CD200 expression in IL-4-deficient mice results in increased neuroinflammation in response to lipopolysaccharide.
Maintenance of the balance between pro- and anti-inflammatory cytokines in the brain, which is affected by the activation state of microglia, is important for maintenance of neuronal function. Evidence has suggested that IL-4 plays an important neuromodulatory role and has the ability to decrease lipopolysaccharide-induced microglial activation and the production of IL-1beta. We have also demonstrated that CD200-CD200R interaction is involved in immune homeostasis in the brain. ⋯ Furthermore, CD200 was decreased in neurons prepared from IL-4(-/-) mice, whereas stimulation with IL-4 enhanced CD200 expression. Importantly, neurons prepared from wildtype, but not from IL-4(-/-), mice attenuated the lipopolysaccharide-induced increase in pro-inflammatory cytokine production by glia. These findings suggest that the neuromodulatory effect of IL-4, and in particular its capacity to maintain microglia in a quiescent state, may result from its ability to upregulate CD200 expression on neurons.
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Brain Behav. Immun. · Jul 2009
ReviewSex and gender in psychoneuroimmunology research: past, present and future.
To date, research suggests that sex and gender impact pathways central to the foci of psychoneuroimmunology (PNI). This review provides a historical perspective on the evolution of sex and gender in psychoneuroimmunology research. ⋯ We provide an overview of the literature of sex and gender differences in brain structure and function, sex steroids, gender role identification, hypothalamic-pituitary-adrenal axis function, genetics, immunology and cytokine response. Specific examples shed light on the importance of attending to sex and gender methodology in PNI research and recommendations are provided.
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Brain Behav. Immun. · Jul 2009
Comparative StudyEffects of gender and dementia severity on Alzheimer's disease caregivers' sleep and biomarkers of coagulation and inflammation.
Being a caregiver for a spouse with Alzheimer's disease is associated with increased risk for cardiovascular illness, particularly for males. This study examined the effects of caregiver gender and severity of the spouse's dementia on sleep, coagulation, and inflammation in the caregiver. ⋯ The findings suggest that males caring for spouses with more severe dementia experience more disturbed sleep and have greater coagulation, the latter being associated with the disturbed sleep. These findings may provide insight into why male caregivers of spouses with Alzheimer's disease are at increased risk for illness, particularly cardiovascular disease.