Brain, behavior, and immunity
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Brain Behav. Immun. · Nov 2016
NOX2 drives M1-like microglial/macrophage activation and neurodegeneration following experimental traumatic brain injury.
Following traumatic brain injury (TBI), activation of microglia and peripherally derived inflammatory macrophages occurs in association with tissue damage. This neuroinflammatory response may have beneficial or detrimental effects on neuronal survival, depending on the functional polarization of these cells along a continuum from M1-like to M2-like activation states. The mechanisms that regulate M1-like and M2-like activation after TBI are not well understood, but appear in part to reflect the redox state of the lesion microenvironment. ⋯ NOX2 deficiency also promotes M2-like activation after CCI, through increased IL-4Rα signaling in infiltrating macrophages, suggesting that NOX2 acts as a critical switch between M1- and M2-like activation states after TBI. Administration of gp91ds-tat to wild-type CCI mice starting at 24h post-injury reduces deficits in cognitive function and increased M2-like activation in the hippocampus. Collectively, our data indicate that increased NOX2 activity after TBI drives M1-like activation that contributes to inflammatory-mediated neurodegeneration, and that inhibiting this pathway provides neuroprotection, in part by altering M1-/M2-like balance towards the M2-like neuroinflammatory response.
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Brain Behav. Immun. · Aug 2016
NLRP3 inflammasome activation mediates estrogen deficiency-induced depression- and anxiety-like behavior and hippocampal inflammation in mice.
Decline of estrogen level is associated with an increase in mood disturbances such as depression and anxiety. Our previous study showed that increased levels of inflammatory cytokines in hippocampus contribute to estrogen deficiency-induced depression-like behavior in rodents. Since the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases, we explored whether NLRP3 inflammasome is involved in affective disorders caused by estrogen deficiency. ⋯ Our study suggests that estrogen deficiency results in NLRP3 inflammasome activation, thereby leading to neuroinflammation in hippocampus and depression and anxiety. Estrogen modulation of inflammation in hippocampus and depression- and anxiety-like behavior is ERβ dependent. NLRP3 inflammasome could be the potential therapeutic target for estrogen deficiency-related affective disorders.
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Brain Behav. Immun. · Aug 2016
Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study.
The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning. ⋯ Compared to HCs, the decreased NAA+NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.
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Brain Behav. Immun. · Aug 2016
Case ReportsAnti-NMDAR antibodies in new-onset psychosis. Positive results in an HIV-infected patient.
The role of neuronal surface autoantibodies (NSAs) in non-encephalitic psychosis is of recent and controversial interest. Most of the studies relating NSAs with psychosis are retrospective and only focused on the N-methyl-d-aspartate glutamate receptor (NMDAR). Our goal was to evaluate the prevalence of IgG antibodies against the NMDAR NR1 subunit (NMDAR-Abs) along with five additional NSAs in 61 first psychotic episode patients and 47 matched controls. ⋯ This study shows that patients presenting with clinically incomplete forms of anti-NMDAR encephalitis, with predominant or isolated psychiatric symptoms, can remain undetected if no ancillary tests are performed. To improve patient diagnosis and treatment of individuals with a first psychotic episode, more detailed neurological examinations might be needed. Further studies are required to better clarify the role of NSAs in the neuropsychiatric effects of HIV infection.
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Brain Behav. Immun. · Aug 2016
Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication.
Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. ⋯ Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis.