The objective of this study was to explore the association between the P2X7 purinergic receptor (P2X7R) and neuroinflammation using a preclinical model of acute bipolar mania. We analyzed the ...modulatory effects of P2X7R agonist (3′-O-(4-benzoyl)benzoyl-adenosine 5′-triphosphate, BzATP) and antagonists (brilliant blue, BBG and 3-5-(2,3 dichlorophenyl)-1H-tetrazol-1-ylmethylpyridine hydrochloride, A438079) on assessments related to behavior (locomotor activity), neuroinflammation (interleukin-1 beta, IL-1β; tumor necrosis factor alpha, TNF-α; and interleukin- 6, IL-6), oxidative stress (thiobarbituric acid reactive substances, TBARS) and neuroplasticity (brain-derived neurotrophic factor, BDNF) markers in a pharmacological model of mania induced by acute and chronic treatment with D-amphetamine (AMPH) (2 mg/kg) in mice. An apparent lack of responsiveness to AMPH was observed in terms of the locomotor activity in animals with blocked P2X7R or with genetic deletion of P2X7R in knockout (P2X7R
−/−
) mice. Likewise, P2X7R participated in the AMPH-induced increase of the proinflammatory and excitotoxic environment, as demonstrated by the reversal of IL-1β, TNF-α, and TBARS levels caused by P2X7R blocking. Our results support the hypothesis that P2X7R plays a role in the neuroinflammation induced by AMPH in a preclinical model of mania, which could explain the altered behavior. The present data suggest that P2X7R may be a therapeutic target related to the neuroinflammation reported in bipolar disorder.
To test the hypothesis that genetic variations of cannabinoid receptors contribute to the pathophysiology of cognitive deficits in schizophrenia.
In this genetic association case-control study, ...cannabinoid receptor polymorphisms CNR1 rs12720071 and CNR2 rs2229579 were tested for association with neurocognitive performance in 69 patients with schizophrenia and 45 healthy controls. Neurocognition was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS).
We found a consistent association between CNR1 rs12720071 polymorphism and the cognitive performance of patients in several cognitive domains. Patients with C/C polymorphism presented significantly worse performance in motor speed, verbal fluency, attention/processing speed and reasoning/problem solving.
Although limited, our data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia.
Exercise can be an effective treatment for depression. Although the efficacy of exercise is well established, little is known concerning the biological changes associated with the antidepressant ...effects of exercise. A randomized, controlled trial was conducted to evaluate the effects of adding exercise to the usual treatment on the thiobarbituric acid-reactive substances (TBARS) and brain-derived neurotrophic factor (BDNF) serum levels of severely depressed inpatients. Twenty-six participants were randomized to an exercise group (
n
= 15, exercise + treatment as usual) or a control group (
n
= 11, treatment as usual). The participants in the exercise group completed a targeted dose of 16.5 kcal/kg/week of aerobic exercise, three times per week, throughout their hospitalizations. The control group did not exercise during their hospitalizations. The mean hospitalization length was of 21.63 (4.5) × 23.82 (5.7) days for exercise and control groups, respectively. The exercise group performed a median of nine sessions. After adjusting for previous tobacco use, a significant group × time interaction was found for TBARS serum levels (
p
= 0.02). A post hoc Bonferroni test revealed differences between the exercise and control groups at discharge. A significant time effect (
p
< 0.001) but no group × time interaction was found (
p
= 0.13) for BDNF serum levels. Adding exercise to the usual treatment of severely depressed inpatients decreases the TBARS serum levels of severely depressed inpatients after 3 weeks. Adding exercise had no additional effects on BDNF serum levels.
Bipolar disorder (BD) is a severe chronic psychiatric disorder that has been associated with cellular dysfunctions related to mitochondria, neurotrophin levels, and oxidative stress. Evidence has ...shown that endoplasmic reticulum (ER) stress may be a common pathway of the cellular changes described in BD. In the present study we assessed unfolded protein response (UPR) and the effects of this cellular process on lymphocytes from patients with BD. We also evaluated whether the stage of chronicity of BD was associated with changes in UPR parameters. Cultured lymphocytes from 30 patients with BD and 32 age- and sex-matched controls were treated with tunicamycin, an ER stressor, for 12 or 24 h to measure levels of UPR-related proteins (GRP78, eIF2α-P, and CHOP) using flow cytometry, and for 48 h to analyse ER stress-induced cell death. In healthy controls but not in patients we found an increase in levels of GRP78, eIF2α-P, and CHOP after ER stress induction. In addition, tunicamycin-induced cell death was significantly higher in patients compared to controls. More importantly, early-stage patients did not differ from controls while the late-stage patients showed an impaired ER stress response. Thus, dysfunction in ER-related stress response may be associated with decreased cellular resilience in BD and illness progression.
Today, the need to dispose of a huge amount of ceramic industrial waste represents an important problem for production plants. Contextually, it is increasingly difficult to retrieve new mineral ...resources for the realization of building materials. Reusing ceramic industrial waste as precursors for building blocks/binders, exploiting their aluminosilicate composition for an alkaline activation process, could solve the problem. This chemical process facilitates the consolidation of new binders/blocks without thermal treatments and with less CO2 emissions if compared with traditional cements/ceramics. The alkali-activated materials (AAMs) are today thought as the materials of the future, eco-sustainable and technically advanced. In this study, six different kind of industrial ceramic waste are compared in their chemical and mineralogical composition, together with their thermal behaviour, reactivity in an alkaline environment and surface area characteristics, with the aim of converting them from waste into new resources. Preliminary tests of AAM synthesis by using 80%–100% of ceramic waste as a precursor show promising results. Workability, porosity and mechanical strengths in particular are measured, showing as, notwithstanding the presence of carbonate components, consolidated materials are obtained, with similar results. The main factors which affect the characteristics of the synthetized AAMs are the precursors’ granulometry, curing temperature and the proportions of the activating solutions.
Aged pressure sensitive tapes (PSTs) can compromise the integrity and readability of drawings and paper artworks. Typically, PSTs on contemporary artifacts are difficult to remove owing to ...degradation processes and to the intrinsic sensitiveness of paper, inks and dyes to the solvents and tools used in the traditional conservation practice. Alternatively, we provide here a critical overview and expansion on the use of two recently developed methodologies for the removal of PSTs, based on the confinement of cleaning fluids in retentive gels. Various combinations of PSTs backings and adhesives were addressed on paper mock-ups containing different types of artistic media (inks, dyes), monitoring the ability of a hydrogel and an organogel to gradually exchange, respectively, an oil-in-water microemulsion or diethyl carbonate through the PSTs backings, swelling the adhesive layers and enabling safe PST removal. It was shown that the two methodologies are complementary as they target the removal of tapes with different components. In all cases, selective tape removal was carried out without uncontrolled bleeding of inks or transport of dissolved matter through the paper matrix, thanks to the retentiveness of the gels. The two cleaning systems were then assessed on four completely different artworks on paper, where they proved to be versatile tools to remove aged PSTs, or re-adhere detackified tapes that were part of the original artwork. Overall, the two methodologies complement each other and allowed overcoming the limitations of traditional cleaning approaches.
Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide ...care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers.
The cognitive measures of 17 young (31-58 years) and 18 old (63-84 years) caregivers and of 17 young (37-57 years) and 18 old (62-84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum.
Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups.
Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.
Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are ...pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis.
Streptococcus pneumoniae
is a common cause of bacterial meningitis, with a high mortality rate and neurological sequelae. In contrast, folic acid plays an important role in neuroplasticity and the ...preservation of neuronal integrity. In the present study, we evaluated the influence of folic acid on memory, oxidative damage, enzymatic defence, and brain-derived neurotrophic factor (BDNF) expression in experimental pneumococcal meningitis. In animals that received folic acid at a dose of 10 or 50 mg, there was a reduction in both crossing and rearing during an open-field task compared with the training session, demonstrating habituation memory. During a step-down inhibitory avoidance task, there was a difference between the training and the test sessions, demonstrating aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group; however, adjuvant treatment with 10 mg of folic acid increased BDNF expression, decreased lipid peroxidation, protein carbonylation, nitrate/nitrite levels, and myeloperoxidase activity and increased superoxide dismutase activity. In frontal cortex adjuvant treatment with 10 mg of folic acid decreased lipid peroxidation and protein carbonylation. There is substantial interest in the role of folic acid and related pathways in nervous system function and in folic acid’s potential therapeutic effects. Here, adjuvant treatment with vitamin B9 prevented memory impairment in experimental pneumococcal meningitis.
Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the ...serum from BD patients could modulate the phenotype of cultured macrophages.
Eighteen subjects with BD and five healthy individuals were included in this study. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate (PMA) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative PCR.
Macrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1β (6.40±3.47 and 9.04±5.84 vs. 0.23±0.11;
＜0.05) and tumor necrosis factor-α (2.23±0.91 and 2.03±0.45 vs. 0.62±0.24;
=0.002 and
=0.004, respectively) compared to euthymic group (there was no difference between euthymic and controls). In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29±0.20 vs. 1.86±1.61;
=0.006) and CXCL10 expression (0.36±0.15 and 0.86±0.24 vs. 1.83±0.88;
＜0.000 and
=0.04) compared to the euthymia group.
Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of BD.
PDF
