Brain, behavior, and immunity
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Brain Behav. Immun. · Aug 2011
Multicenter StudyFatigue, depressive symptoms, and anxiety from adolescence up to young adulthood: a longitudinal study.
Fatigue is a common complaint among adolescents. We investigated the course of fatigue in females during the transition from adolescence to young adulthood and examined psychological, immunological, and life style risk factors for development of fatigue and chronic fatigue syndrome (CFS)-related symptoms. Six hundred and thirty-three healthy females (age 14.63±1.37 years) filled out questionnaires measuring fatigue severity, depressive symptoms, anxiety, chronic fatigue syndrome (CFS)-related symptoms, sleep features, and life style characteristics at baseline and 4½ years thereafter. ⋯ The rise in total number of CFS-related symptoms at follow up was predicted by anxiety and decreased physical activity during adolescence. Sleep and substance use were associated with fatigue severity and anxiety and depression. In conclusion, vulnerability to develop fatigue and associated symptoms in young adulthood can to a certain extent be identified already years before the manifestation of complaints.
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Brain Behav. Immun. · Aug 2011
Effects of palmitoylethanolamide on release of mast cell peptidases and neurotrophic factors after spinal cord injury.
Spinal cord injury (SCI) has a significant impact on quality of life, expectancy, and economic burden, with considerable costs associated with primary care and loss of income. The complex pathophysiology of SCI may explain the difficulty in finding a suitable therapy for limiting neuronal injury and promoting regeneration. Although innovative medical care, advances in pharmacotherapy have been limited. ⋯ Moreover, PEA treatment significantly reduced the activation of microglia and astrocytes expressing cannabinoid CB(2) receptor after SCI. Importantly, the protective effect of PEA involved changes in the expression of neurotrophic factors, and in spinal cord dopaminergic function. Our results enhance our understanding about mechanisms related to the anti-inflammatory property of the PEA suggesting that this N-acylethanolamine may represent a crucial therapeutic intervention both diminishing the immune/inflammatory response and promoting the initiation of neurotrophic substance after SCI.
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Brain Behav. Immun. · Jul 2011
The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system.
Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. ⋯ These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.
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Brain Behav. Immun. · Jun 2011
Altered hippocampal synaptic transmission in transgenic mice with astrocyte-targeted enhanced CCL2 expression.
Elevated expression of neuroinflammatory factors in the central nervous system (CNS) contributes to the cognitive impairment in CNS disorders such as injury, disease and neurodegenerative disorders. However, information on the role of specific neuroimmune factors in normal and abnormal CNS function is limited. In this study, we investigated the effects of chronic exposure to the chemokine CCL2 on hippocampal synaptic function at the Schaffer collateral-CA1 synapse, a synapse that is known to play an important role in cognitive functions such as memory and learning. ⋯ Two forms of short-term synaptic plasticity (post-tetanic potentiation and short-term potentiation) thought to be important cellular mechanisms of short-term memory were enhanced in hippocampal slices from CCL2 transgenic mice compared to non-transgenic hippocampal slices, whereas long-term synaptic plasticity (LTP), which is critical to long-term memory formation, was not altered. Western blot analysis of hippocampus from the CCL2 transgenic mice and non-transgenic mice showed no change in level of neuronal specific enolase, a neuronal specific protein, GFAP, an astrocyte specific protein, and several synaptic proteins compared with non-transgenic littermate controls. These results show that CCL2, which is known to be chronically produced at elevated levels within the CNS in a number of CNS disorders, can significantly alter hippocampal function and implicate a role for CCL2 in the cognitive dysfunction associated with these CNS disorders.
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Brain Behav. Immun. · May 2011
Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors.
Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. ⋯ Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.