Neuroimmunomodulation最新文献

Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. Interleukin-32 (IL-32) is a proinflammatory cytokine that is essential in activating innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia.

Material and methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, amphiphysin, SOX1, Zic4, ITPR1, CARP, glutamic acid decarboxylase GAD, recoverin, titin, and ganglioside antigens was measured by the indirect immunofluorescence method.

Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. The frequency of autoantibodies against GAD and RI antigens in patients with schizophrenia was significantly higher than in the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for RI antigen. Autoantibodies were also positive in 2 patients for CV2, 1 patient for Hu, and 1 patient for CARP. Negative results were reported for other antigens.

Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibodies against GAD and RI antigens may be a reflection of immune system dysregulation in patients with schizophrenia.

Introduction: The prenatal/perinatal exposure to infections may trigger neurodevelopmental alterations that lead to neuropsychiatric disorders such as autism spectrum disorder (ASD). Previous evidence points to long-term behavioral consequences, such as autistic-like behaviors in rodents induced by lipopolysaccharide (LPS) pre- and postnatal (PN) exposure during critical neurodevelopmental periods. Additionally, sex influences the prevalence and symptoms of ASD. Despite this, the mechanisms underlying this influence are poorly understood. We aim to study sex influences in behavioral and neurotrophic/inflammatory alterations triggered by LPS neonatal exposure in juvenile mice at an approximate age of ASD diagnosis in humans.

Methods: Swiss male and female mice on PN days 5 and 7 received a single daily injection of 500 μg/kg LPS from Escherichia coli or sterile saline (control group). We conducted behavioral determinations of locomotor activity, repetitive behavior, anxiety-like behavior, social interaction, and working memory in animals on PN25 (equivalent to 3-5 years old of the human). To determine BDNF levels in the prefrontal cortex and hippocampus, we used animals on PN8 (equivalent to a human term infant) and PN25. In addition, we evaluated iba-1 (microglia marker), TNFα, and parvalbumin expression on PN25.

Results: Male juvenile mice presented repetitive behavior, anxiety, and working memory deficits. Females showed social impairment and working memory deficits. In the neurochemical analysis, we detected lower BDNF levels in brain areas of female mice that were more evident in juvenile mice. Only LPS-challenged females presented a marked hippocampal expression of the microglial activation marker, iba-1, and increased TNFα levels, accompanied by a lower parvalbumin expression.

Discussion/conclusion: Male and female mice presented distinct behavioral alterations. However, LPS-challenged juvenile females showed the most prominent neurobiological alterations related to autism, such as increased microglial activation and parvalbumin impairment. Since these sex-sensitive alterations seem to be age-dependent, a better understanding of changes induced by the exposure to specific risk factors throughout life represents essential targets for developing strategies for autism prevention and precision therapy.

Introduction: In recent years, according to the literature, the problem of mild traumatic brain injury (mTBI) has become more and more urgent. Compared to moderate to severe craniocerebral trauma, mTBI occurs in a far greater number of people. The delayed sequelae caused by a single mTBI or multiple mTBIs are a significant public health problem.

Methods: A weight-drop model was used for the formation of mTBI. A metal rod weighing 337 g with a blunt tip of 3 mm diameter was uplifted at 8 cm height and held by a lever. The trauma was created by lowering the lever and the rod and free-dropping onto the rat skull. In the cerebral cortex of experimental animals, we analyzed the level of microglial activity (Iba-1-positive system) and the expression of pro-inflammatory markers (IL1β, IL6, and CD86). Also, the expression level of the endocannabinoid system receptor (cannabinoid receptor type 1 [CB1]) was assessed in brain samples.

Results: Experiments have shown that mTBI increases (1) the amount of microglia (iba-1) activated by the pro-inflammatory pathway (CD86); (2) the level of pro-inflammatory cytokines IL1β and IL6; and (3) CB1R activity.

Conclusion: Overall, the results of this study indicate that mTBI induces a sustained neuroinflammatory response.

n/a.

Introduction: Glioma is the most aggressive and malignant type of tumors among primary intracranial tumors. miR-433-3p has been verified to be correlated with the formation and progression of many types of cancers.

Methods: In this study, the effects of miR-433-3p and AJUBA on the proliferation, migration, and invasion of glioma and the molecular mechanisms were investigated. We analyzed bioinformatics databases and conducted cell biology experiments to determine that compared with adjacent tissue and normal cells, the expression level of miR-433-3p in glioma tissue and cells was lower, while the expression level of AJUBA was higher. Overexpressing miR-433-3p could significantly inhibit the proliferation, migration, and invasion of glioma cells and promote cell apoptosis.

Results: In addition, after overexpressing miR-433-3p and AJUBA, it was found that overexpressing AJUBA could attenuate the inhibitory effect of overexpressing miR-433-3p on the proliferation, migration, and invasion of glioma cells, which suggested that miR-433-3p regulated the biological function of glioma by downregulating AJUBA expression.

Conclusion: These results proved that miR-433-3p could target to inhibit the expression of AJUBA, thus inhibiting the biological function and malignant progression of glioma.

Objective: This study aims to construct a prognostic model based on the different immune infiltration statuses of the glioma samples.

Methods: Glioma-associated dataset was assessed from The Cancer Genome Atlas database. Hierarchical cluster analysis was performed to classify the glioma samples. Single-sample gene set enrichment analysis was introduced to the glioma samples for immune infiltration analysis. Kaplan-Meier survival analysis was applied to evaluate patients' prognoses. The differentially expressed genes (DEGs) between different sample groups were screened using limma package. Univariate Cox, LASSO Cox, and multivariate Cox regression analyses were employed to construct the prognostic model. The prediction performance of the model was examined by plotting a receiver-operating characteristic (ROC) curve, and GSEA was introduced to screen the differently activated pathways between high- and low-risk groups.

Results: The glioma samples were classified into 3 clusters where the different immune infiltration and survival statuses were presented among the clusters. 123 immune-related DEGs were screened from the differential expression analyses, and based on these DEGs, an 8-gene prognostic model was constructed. The ROC curve exhibited an optimal performance of the prognostic model, and GSEA showed that ECM-receptor interaction, complement and coagulation cascades, cytokine receptor pathways, and viral protein interaction with cytokine were differently activated between the two risk groups.

Conclusion: The current study screened an immune-associated gene set by classifying and differential analysis, followed by constructing an 8-gene prognostic model based on the screened genes.

Objective: At present, studies on lymphocytes are mostly conducted on CD19+ B cells and CD27+ B cells in neuromyelitis optica spectrum disorders (NMOSDs), but the exact changes in lymphocyte subsets (CD19+ B cells, CD3+ T cells, CD4+ Th cells, CD8+ Ts cells, the CD4+/CD8+ ratio, and NK [CD56+ CD16] cells) have rarely been studied. This study aimed to assess lymphocyte subset changes in patients with NMOSD.

Methods: We performed a cross-sectional study of consecutive patients with acute NMOSD (n = 41), chronic NMOSD (n = 21), and healthy individuals (n = 44). Peripheral blood samples were obtained upon admission, and lymphocyte subsets were analyzed by flow cytometry. Levels of lymphocyte subsets among 3 groups were compared and its correlation with the length of spinal cord lesions was analyzed.

Results: The levels of peripheral blood CD19+ B cells were significantly higher in patients with acute and chronic NMOSD than in healthy controls (HCs) (17.91 ± 8.7%, 13.08 ± 7.562%, and 12.48 ± 3.575%, respectively; p < 0.001) and were positively correlated with the length of spinal cord lesions in acute NMOSD (r = 0.433, p < 0.05). The peripheral blood CD4+/CD8+ ratio was significantly lower in patients with acute NMOSD and chronic NMOSD than in HCs (1.497 ± 0.6387, 1.33 ± 0.5574, and 1.753 ± 0.659, respectively; p < 0.05), and the levels of peripheral blood NK (CD56+ CD16) cells were significantly lower in patients with acute and chronic NMOSD than in HCs (13.6 ± 10.13, 11.11 ± 7.057, and 14.7 [interquartile range = 9.28], respectively; p < 0.01).

Conclusions: The levels of certain subsets of peripheral blood lymphocytes are associated with disease status in NMOSD.

Background: Elevation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signaling can suppress intracerebral hemorrhage (ICH)-induced neurological impairments. As an isoquinoline alkaloid, Berberine exerts neuroprotective effects in neurological disease models with activated AMPK/PGC1α signaling.

Aim: We aim to study the effect of Berberine on ICH-induced brain injury and explore the potential molecular mechanism.

Methods: ICH model was established in mice through intracerebral injection of autologous whole blood, followed by treatment with Berberine. Neurological impairments were assessed by the modified neurological severity score and behavioral assays. Brain edema and blood-brain barrier (BBB) integrity were assessed by water content in the brain, amount of extravasated Evans blue, and BBB tight junction components. Neuroinflammatory responses were assessed by inflammatory cytokine levels. AMPK/PGC1α signaling was examined by AMPK mRNA expression and phosphorylated AMPK and PGC1α protein levels.

Results: Berberine (200 mg/kg) attenuated ICH-induced neurological deficits, motor and cognitive impairment, and BBB disruption. Berberine also suppressed ICH-induced inflammatory responses indicated by reduced production of inflammatory cytokines. Finally, Berberine drastically elevated AMPK/PGC1α signaling in the hemisphere of ICH mice.

Conclusion: Our findings suggest that Berberine plays an important neuroprotective role against ICH-induced neurological impairments and BBB injury, probably by inhibition of inflammation and activation of AMPK/PGC1α signaling.

Introduction: This article purposed to detect the function of the HOTAIR and HOTAIR/microRNA-129-5p (miR-129-5p) axis on the isoflurane (ISO)-injured cells and rat, and propounded a novel perspective in exploring the molecular pathogenesis of ISO damage.

Methods: The expression of HOTAIR and miR-129-5p was tested by quantitative real-time PCR. The viable cells were identified using MMT, and the apoptotic cells were provided by flow cytometry. The concentration of proinflammatory indicators was revealed by enzyme-linked immunosorbent assay kits. The function of HOTAIR on oxidative stress was detected by commercial kits. A luciferase assay was performed to confirm the relationship between miR-129-5p and HOTAIR. The Morris water maze test was conducted to elucidate the cognition of SD rats.

Results: The expression of HOTAIR was enhanced and the expression of miR-129-5p was lessened in the ISO-evoked SD rats and HT22 cells. The interference of HOTAIR reversed the injury of ISO on cell viability, apoptosis, inflammation, and oxidative stress. Besides, HOTAIR might be a target ceRNA of miR-129-5p. MiR-129-5p abrogated the function of silenced HOTAIR on cell viability, cell apoptosis, inflammation, and oxidative stress. Moreover, in vivo, the intervention of HOTAIR reversed the influence of ISO on cognition and oxidative stress by binding miR-129-5p.

Discussion/conclusion: Lowly expressed HOTAIR contributed to the recovery of the ISO-injured HT22 cell model from the abnormal viability, apoptosis, inflammation, and oxidative stress by regulating miR-129-5p. miR-129-5p mediated the function of HOTAIR on cognition and oxidative balance in the ISO-managed SD rat model.

Introduction: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described steroid-responsive meningoencephalomyelitis positive for cerebrospinal fluid (CSF) anti-GFAP antibody. Area postrema syndrome (APS) involves intractable hiccups, nausea, and vomiting, which is caused by medulla oblongata (MO) impairment. APS is a characteristic symptom of aquaporin-4 (AQP4) autoimmunity, and it helps to differentiate between AQP4 and GFAP autoimmunity. Conversely, although 6 cases of autoimmune GFAP astrocytopathy with APS and MO lesions have been reported, the association between GFAP autoimmunity and APS is unclear. We report the case of a patient with autoimmune GFAP astrocytopathy presenting with APS-like symptoms without MO lesions and discuss the mechanisms underlying the symptoms.

Methods: CSF anti-GFAP antibody was detected using cell-based assays and immunohistochemical assays.

Results: A 54-year-old Japanese man developed persistent hiccups, intermittent vomiting, fever, anorexia, and inattention. Brain magnetic resonance imaging (MRI) showed periventricular lesions with radial linear periventricular enhancement, suggesting autoimmune GFAP astrocytopathy. However, no obvious MO lesions were identified on thin-slice images. Spinal cord MRI revealed hazy lesions with patchy enhancement along the cervical and thoracic cord. CSF analysis demonstrated inflammation, with positive results for anti-GFAP antibodies. Anti-AQP4 antibodies in the serum and CSF were negative. Esophagogastroduodenoscopy revealed gastroparesis and gastroesophageal reflux disease, and vonoprazan, mosapride, and rikkunshito were effective only against persistent hiccups. Steroid therapy was initiated, allowing clinical and radiological improvements. Repeated MRIs demonstrated no obvious MO lesions.

Conclusion: This report suggests that autoimmune GFAP astrocytopathy presents with APS-like symptoms without obvious MO lesions. The possible causes of hiccups were gastroparesis and cervical cord lesions. Gastroesophageal reflux disease was not considered a major cause of the hiccups. Intermittent vomiting appeared to be associated with gastroparesis, cervical cord lesions, and viral-like symptoms. Testing for anti-GFAP antibodies should be considered in patients with APS-like symptoms in the context of typical clinical-MRI features of autoimmune GFAP astrocytopathy.