MBP Levels Research Articles

A novel long noncoding RNA lnc158 promotes the differentiation of mouse neural precursor cells into oligodendrocytes by targeting nuclear factor-IB.

Long noncoding RNAs have been implicated in oligodendrocyte myelination and oligodendrocyte maturation, but their roles in normal oligodendrocyte differentiation are not fully defined. Here, we report a novel nonprotein-coding RNA, named lnc158, discovered in mouse oligodendrocytes identified in subependymal ventricular zone tissue by single-cell RNA sequencing. Lnc158 is an endogenous antisense transcript of nuclear factor-IB (NFIB) and complementary to 3' untranslated region of NFIB mRNA. NFIB is a member of the nuclear factor-I family and is essential in the development of many organs such as brains and lungs. We found that lnc158 transcripts serve a biological function by regulating the transcription level of the NFIB coding gene in neural stem cells. Overexpression of lnc158 increased the expression of NFIB mRNA and knockdown of lnc158 decreased the expression of NFIB mRNA, suggesting that NFIB is regulated positively by lnc158. Further analyses showed that overexpression of lnc158 in neural stem cells induced a modest increase in CNP, MBP, MAG, and OSP mRNA level, and enhanced induction of differentiation along the lineage of oligodendrocytes. These results together imply that lnc158 positively modulates the transcription level of NFIB mRNA, leading to the enhanced induction of oligodendrocytes.

Autoantibodies to myelin proteins as biomarkers to identify nervous system injuries in Gulf War Illness and other neuromuscular disorders

Abstract A study on veterans with Gulf War Illness (GWI) from Madison VA Hospital demonstrated a widespread disruption of damages to the white matter using magnetic resonance brain imaging suggesting a cause of prolonged chronic musculoskeletal pain. We hypothesized that exposure to various chemicals could cause delayed neurotoxicity and that myelin is an important white matter component, which play a critical role in neural function and plasticity. Any disruption to myelin may result in reduced brain connectivity, musculoskeletal pain, and cognitive dysfunction. Since myelin is composed of various proteins, dysregulation or damage over a period will form a distinguishable biomarker in CSF and in serum/plasma. Further, continued damage could elicit an immune response. With these reasoning, we measured serum/plasma levels of myelin proteins and autoantibodies specific to myelin proteins by ELISA in Veterans with Gulf War Illness (GWI) and other patients with neuronal disorders (Multiple Sclerosis (MS), Parkinson’s disease (PD), mild Traumatic Brain Injury (TBI), Flight Crews with chronic pain and veterans with Chronic Fatigue Syndrome (CFS) and Lupus (SLE)). We quantitated several myelin proteins (MPZ, MAG, MBP MOG, MOBP, PMP2, and NF155) to determine the intensity of disruption. Autoantibody levels in MS patients were used as positive control and since all the samples (n=10) tested showed the highest level of IgG specific autoantibodies compared to other cohorts. Significantly increased levels of NF155, MOG, MOBP, and MAG were observed among all groups compared to controls (p<0.001). Elevated levels of MPZ and PMP2 characterized PD and SLE (p<0.01) and GWI veterans showed elevated levels of MBP compared CFS and healthy cohorts.

Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy for Acute Lymphoblastic Leukemia

Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only. To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms. This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol. Patients provided CSF samples after diagnosis and throughout treatment. At 5 or more years after the diagnosis, 138 (69.7%) of 198 eligible survivors participated in long-term follow-up assessments. Children were treated from June 1, 2000, through October 31, 2010. Follow-up was completed on October 21, 2014, and data were analyzed from August 1, 2015, through September 30, 2016. Plasma concentration of high-dose intravenous methotrexate sodium and number of triple intrathecal chemotherapy injections. The CSF samples were assayed at 5 points from diagnosis to reinduction for biomarkers of myelin degradation (myelin basic protein [MBP]), neuronal damage (nerve growth factor [NGF] and total and phosphorylated tau protein), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuroinflammation (chitotriosidase). DNA was genotyped for polymorphisms in drug metabolism, oxidative stress, and neurodevelopment. Leukoencephalopathy was evaluated by brain imaging. At 5 or more years after the diagnosis, survivors completed neurocognitive testing and brain imaging of white matter integrity. Among the 235 patients with CSF samples (120 boys [51.1%] and 115 girls [48.9%]; mean [SD] age at diagnosis, 6.8 [4.7] years), MBP and GFAP levels were elevated at baseline and through consolidation. The number of intrathecal injections was positively correlated with NGF level increase at consolidation (r = 0.19; P = .005). Increases in GFAP (risk ratio [RR], 1.23; 95% CI, 1.09-1.40), MBP (RR, 1.06; 95% CI, 1.01-1.11), and total tau (RR, 1.76; 95% CI, 1.11-2.78) levels were associated with a higher risk for leukoencephalopathy and higher apparent diffusion coefficient in frontal lobe white matter 5 years after diagnosis (standardized estimate, 0.05; P < .001). Increase in total tau at consolidation was associated with worse attention (omissions z score estimate, -0.20; P = .04). Glial injury may be present at diagnosis of ALL. Neuronal injury was associated with intrathecal chemotherapy. The CSF biomarkers may be useful in identifying individuals at risk for worse neurologic outcomes, particularly those with genetic susceptibility to poor brain function.

Effects of microRNA-330 on vulnerable atherosclerotic plaques formation and vascular endothelial cell proliferation through the WNT signaling pathway in acute coronary syndrome.

This study is designed to investigate the effects of microRNA (miR)-330 on atherosclerotic plaques formation and vascular endothelial (VE) cell proliferation by targeting MAPK8 through the WNT signaling pathway in rats with acute coronary syndrome (ACS). Expression of hemodynamic variables were tested. Rats were allocated into control, blank, negative control (NC), miR-330 mimic, miR-330 inhibitor, DDK-1, miR-330 inhibitor + DDK-1 groups. ELISA was used to evaluate the expression of TC, TG, LDL-C, hs-CRP, IL-6, IL-10, TNF-α, and SAA. Immunohistochemistry, reverse transcription quantitative polymerase chain reaction and Western blotting were used for expression of VEGF, MAPK8, WNT1, β-catenin, GSK-3β, p-GSK-3β, CyclinD1, MMP-9, IL-6, and IL-8. MTT assay and flow cytometry for cell proliferation and apoptosis. Compared with the control group, other groups had lower levels of SBP, DBP, MBP, LVSP, and miR-330, higher levels of HR, LVEDP, TC, TG, LDC-C, hs-CRP, IL-6, IL-10, TNF-α, SAA, higher positive protein expression rates of MAPK8, VEGF, and MMP-9, elevated WNT1, β-catenin, GSK-3β and CyclinD1, and reduced cell proliferation. MAPK8-3'-UTR was targeted by miR-330. Compared with the blank group, the miR-330 mimic and DDK-1 groups had higher levels of SBP, DBP, MBP, LVSP, lower levels of HR, LVEDP, TC, TG, LDC-C, hs-CRP, IL-6, TNF-α, SAA, elevated IL-10, decreased positive protein expression rates of MAPK8 and VEGF, raised cell proliferation and reduced cell apoptosis rates. We conclude that overexpressed miR-330 suppresses atherosclerotic plaques formation while promotes VE cell proliferation by targeting MAPK8 through the WNT signaling pathway in ACS rats.

EGFP transgene: a useful tool to track transplanted bone marrow mononuclear cell contribution to peripheral remyelination.

Bone marrow mononuclear cells (BMMC) constitute a heterogeneous population with potential to promote tissue regeneration. For this reason, this cell fraction has recently become a therapeutic alternative to mesenchymal stem cells, as culture is not required and phenotypic transformations can be hence avoided. In this work, and in order to attain long-lasting cell labeling and study longer survival times, we used BMMC isolated from adult transgenic rats expressing GFP to reproduce our wild type model and evaluate their remyelination ability in a reversible model of Wallerian degeneration. RT-PCR and flow cytometry analysis confirmed that cells isolated from the transgenic strain exhibited similar expression levels of markers specific to multipotent progenitors (CD34, CD90 and CD105) and Schwann cells (MPZ, MBP, S100β and p75NTR) compared to wild type BMMC. BMMC expressing GFP retained their migration capacity, arriving exclusively at the injured nerve. Most importantly, and as detected through long-lasting cell tracking, some of these BMMC settled in the demyelinated area, mingled with endogenous cells, underwent phenotypic changes and colocalized with Schwann cell markers MBP and S100β. Also worth highlighting, transgenic BMMC replicated wild type BMMC effects in terms of MBP organization and levels. On the basis of these findings, BMMC isolated from transgenic animals constitute a useful tool to evaluate their role in peripheral nervous system demyelination-remyelination and the underlying mechanisms.

Analyzing the neuropsychological characteristics and changes in serum markers of patients with chronic cerebral circulation insufficiency.

To investigate the neuropsychological characteristics and changes in CRP, S100B, MBP, HSP-7, and NSE in serum. Sixty-six (66) patients treated in our hospital as CCCI group were chosen for our study, and 90 patients with depression were selected as the depression group. The patients in both groups were examined with CT perfusion, depression, anxiety and cognition evaluation. Their serum CRP, S100B, MBP, HSP-70 and NSE levels were detected. Neuropsychological and serum markers characteristics were compared. The CBF and CBV in bilateral basal ganglia, frontal lobes, greater oval center, brain stem, and left and right regions of occipital lobes of the patients in CCCI group were significantly lower than in the depression group. The HAMD and HAMA scores of CCCI group patients were significantly lower than in the depression group; CCCI group performed better regarding attention, memory, abstract terms and delayed recall. CCCI also had significantly higher total scores than the depression group. Serum CRP, S100B, MBP, HSP-70 and NSE levels in CCCI group were significantly higher than in the depression group. The differences reach statistical significance (p<0.05). CCCI patients who are accompanied by minor depressive disorder have different degrees of cognitive impairment and experience a significant rise in serum CRP, S100B, MBP, HSP-70 and NSE.

Brain-originated peptides as possible biochemical markers of traumatic brain injury in cerebrospinal fluid post-mortem examination.

The release of brain-originated peptides such as tau protein (MAPT), S-100β, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) into the cerebrospinal fluid (CSF) has been positively correlated with head injuries in clinical and basic research. In this study, we wanted to examine if selected CSF biomarkers (GFAP, NFL, and myelin basic protein - MBP) of head injury may be useful in post-mortem examination and diagnosis of forensic cases. The study was carried out using cases of head injury and cases of sudden death (cardiopulmonary failure, no injuries of the head as control group) provided by forensic pathologists at the Department of Forensic Medicine, Medical University of Warsaw. Cerebrospinal fluid was collected within 24 h after death using suboccipital puncture. The concentration of these peptides was compared using an enzyme-linked immunosorbent assay (ELISA). Brain specimens (frontal cortex) were collected during forensic autopsies. Sections were stained immunohistochemically against GFAP, MBP, NF, and amyloid-β precursor protein (APP). As aresult we documented that elevated levels of CSF, GFAP, MBP, and NFL should be considered amarker for severe and moderate traumatic brain injury. Elevated levels of those peptides combined with anegative APP staining point to their role as markers of head trauma with ashorter time span than APP (manner of minutes).

Assessment of Urinary Netrin-1 as a Marker for Progression of Acute Kidney Injury in Critically Ill Patients: Prospective Cohort Study

Background and objective: This study aimed to identify risk factors for progression of AKI in critically ill adult patients in the medical ICU in Alexandria main University Hospitals and to assess urinary netrin-1 as a marker for progression of AKI. Design, setting, participants and measurements: The study included 80 AKI patients who were followed during their ICU stay for primary outcome (progression to severe AKI; KDIGO stage 2 or 3) and secondary outcomes (need for RRT, ICU mortality, length of ICU stay and SCr at the time of discharge from the ICU). All participants were subjected to history taking, full clinical examination and laboratory (routine and specific) investigations. Urine samples were collected for all patients at the time of ICU admission and urinary netrin-1 was measured. Result: Almost one third (33.75%) of the study patients were identified as progressors. Progression was significantly more common among patients with history of CKD (p<0.001), hypotensive patients (p=0.002), septic patients (p=0.041), those who needed RRT (p<0.001) and those who died (p=0.003). Progressors had lower MBP and serum albumin level (p=0.007, 0.008, respectively). They had higher APACHE II score and longer ICU stay (p=0.037, 0.020, respectively). They also had higher basal blood urea, basal SCr and SCr levels at the time of presentation and discharge (p<0.001 for all). The results were similar between progressors and non-progressors, those who received RRT and those who did not and survivors and non-survivors as regards urinary netrin-1 levels. Results of the multivariate analysis revealed that CVD, hypotension and higher basal blood urea level were independent risk factors for AKI progression. Conclusion: The results of this study suggest that history of CKD, hypotension and sepsis are associated with progression of AKI in critically ill patients and that urinary netrin-1 has no significant value as a predictor of AKI progression, need for RRT or ICU mortality.

THE EFFECT OF RESISTANCE BAND TRAINING ON THE MAXIMUM FORCE AND ANAEROBIC POWER OF BOXERS

Study was carried out to examine the effect of application of resistance band in the female boxers on the levels of the anaerobic power and Maximal Bench Press force (MBP). The study was carried out on 12 female subjects, in ages between 19 and 23yo, who are actively engaged in the boxing branch. The subjects were divided into two groups, each consisting of 6 people, as Constant Resistance (CR) and Wavy Resistance (WR). The average age of CR group was 21.33±0.81 years, the average height 169.67±2.06 cm, and the average body weight 65.28±8.95 kg. The average age of WR group was 21.16±0.75 years, the average height 173.50±3.27 cm, and the average body weight 65.56±3.19 kg. In the study, the exercise of resistance band was made by all subjects four days a week for 6 weeks between the hours 9.00-10.00, boxing training for competition period between the hours 18:00–20:00 in evenings. In CR group, the bands in the same color and resistance were used by the method of the black band constant, resistance, in WR group, the bands in different color (red, blue, black) and resistance by the wavy method. Before training, the body weights, and the levels of anaerobic power and MBP levels of both groups were determined. The same measurements were repeated six weeks later. In the statistical analyses of the data obtained, in determining the differences between in-group test and the final test, Paired-sample t-test was used. In determining the difference between two groups, pre-test and final test, independent samples t-test was used. The significance between differences was determined at the level of P<0,05. As a result; as a matter of fact, it can be said that the constant resistance method of CR group is more effective than the wavy resistance method of WR group. Hence, conducting the studies of resistance band that will be conducted specific to branch, using the method of constant resistance, can be more effective. Article visualizations:

Loss of Pericytes in Radiation Necrosis after Glioblastoma Treatments.

Radiation necrosis (RN) in brain tumor patients is often symptomatic, persistent without immediate resolution, and confused with tumor recurrence. Cerebral vascular pericytes are essential for endothelial function, vascular integrity, and angiogenesis. In this study, we showed that the loss of pericytes is involved in the pathogenesis of RN. From a brain tumor tissue repository, we identified three patients since 2011 with pathologically confirmed RN after the standard treatment for glioblastoma (GBM). The RN and their preradiation GBM tissues were serially processed for Western blotting using cell-type-specific antibodies against endothelial (CD31, active RhoA), pericyte [platelet-derived growth factor receptor-beta (PDGFR-β)], alpha-smooth muscle actin (α-SMA), astrocyte (GFAP), myelin sheath protein (MBP), and microglial markers (Iba1). Normal brain tissues from a brain bank were used as normal controls. The expressions of PDGFR-β and α-SMA were remarkably reduced in the RN, compared to those of GBM. However, the levels of CD31 or RhoA were not different between the two groups, which suggest that there was no change in the number of endothelial cells or their cytoskeletal assembly. The RN tissues showed a decreased ratio of pericyte/endothelial markers and an increased level of Iba1 compared to the GBM and even to the normal brain. The levels of GFAP and MBP were not changed in the RN. In the histopathology, the RN tissues showed a loss of markers (PDGFR-β), whereas the GBM tissues had abundant expression of the markers. The loss of pericytes and vascular smooth muscle cells, and the unsupported endothelial cells might be the cause of the leaky blood-brain barrier and tissue necrosis.

Adipose tissue-derived stromal cells (ADSC) express oligodendrocyte and myelin markers, but they do not function as oligodendrocytes.

Mesenchymal cells cultured from the vasculo-stromal fraction of adipose tissue (ADSC) show adult stem cell characteristics and several groups have claimed generating neural cells from them. However, we have observed that many markers commonly used for the identification of neural cells are spontaneously expressed by ADSC in culture. In the present study, we have examined the expression of characteristic oligodendrocyte molecules in cultured ADSC, aiming to test if myelinating cells could be generated from accessible non-neural adult tissues. In basal growth conditions, rat ADSC spontaneously expressed CNPase, MBP, MOG, protein zero, GAP43, Sox10, and Olig2, as shown by immunocytrochemistry and western blot. A small population of cultured ADSC expressed membrane galactocerebroside (O1 antibody), but no cell stained with O4 antibody. RT-PCR analyses showed the expression of CNPase, MBP, DM20, and low levels of Olig2, Sox10, and Sox2 mRNA by rat ADSC. When rat ADSC were treated with combinations of factors commonly used in neural-inducing media (retinoic acid, dbcAMP, EGF, basic FGF, NT3, and/or PDGF), the number of O1-positive cells changed, but in no case, mRNA expression of Sox10 and Olig2 transcription factors approached CNS oligodendrocyte levels. In co-culture with rat dorsal root ganglion neurons, no sign of axonal myelination by rat ADSC was observed. These studies show that the expression of oligodendrocyte traits by cultured ADSC is not a proof of functional competence as oligodendroglia and suggest that in culture conditions, ADSC acquire intermediate, uncommitted phenotypes.

Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage.

Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of Bcl-2 protein increased and expressions of Caspase-3 and Bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins.

Do People Live at Sea Level and the Dead Sea Level Have Different Patterns of Anti-Hypertensive Drugs

Background: people live at various areas of sea level may have different patterns of anti-hypertensive drugs. Such a relation has never been reported in Jordan. Study objectives: the current study investigated how the sea level will impact the prevalence of hypertension in these areas, and how will affect the pharmacological properties of such a population. Methodology: a cross-sectional study design was involved to collect data from study participants. A total of 1000 participants were randomly selected from the two study areas. 500 participants from each. Participants were matched for age and gender. Blood pressure were measured for all participants. Blood samples were withdrawn to investigate the level of angiotensin II. Data was collected through organizing a working excel sheet and was further analyzed through using SPSS version 20. Data was presented as means, standard deviations, frequencies and percentages. The relationships between variables were examined using independent T-test. Significance was measured at an alpha &lt; 0.05. Study findings: the main findings of the present study were that the mean of SBP is significantly higher in the Dead Sea (122.42±10.53 mmHg) than the Sea level area (118.07±11.64 mmHg), (p=0.001). Another significant variable was MBP which its mean was 91.64 ± 8.90 mmHg in the Dead Sea and 89.84 ± 8.72 mm Hg. The difference in the mean was statistically significant (p=0.001). The level of angiotensin II was 8.84 ± 4.65pg/ml in the Dead Sea area and 11.21± 6.05pg/ml in the area of the Sea level. The difference in the mean of the two study areas was not statistically significant (p&gt;0.05). Conclusions: although the level of angiotensin II was not significantly varied between the study areas, but its trend was to be higher in the Sea level area. It was surprised to have higher levels of SBP and MBP in the Dead Sea rather than the Seal level area. It can be implied that the therapeutic options of hypertensive drugs follow different patterns independent of angiotensin II pathways.

Association between urinary phthalates and metabolic abnormalities in obese Thai children and adolescents.

Several endocrine disruptors (including phthalates) are considered to be a cause of obesity. However, the current evidence has not conclusively established an association between phthalates and metabolic abnormalities, especially in children. The objective of the study was to evaluate the association between urinary phthalate metabolites and metabolic abnormalities in obese Thai children and adolescents. This cross-sectional case-control study was conducted in participants aged 7-18 years and divided into two groups: normal weight and overweight/obesity. Spot urine concentrations of two phthalate metabolites (monomethyl phthalate [MMP] and mono-n-buthyl phthalate [MBP]) were measured by high performance liquid chromatography (HPLC). Anthropometric data, including weight, height, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR), were measured and calculated. Fasting plasma glucose, insulin, HbA1c, lipid profiles and hepatic transaminase were analyzed, and insulin resistance indices were calculated. One hundred and fifty-five participants were included. The median MMP level in the normal weight and the overweight/obesity groups were 0 (0, 459.83) and 0 (0, 1623.50) μg/g Cr, respectively (p=0.933). The median MBP level in the normal weight and the overweight/obesity groups were 233.6 (118.1, 633.62) and 206.94 (7.4, 427.7) μg/g Cr, respectively (p=0.083). After adjusting for age, gender and puberty, there was no correlation between MBP and all anthropometric data and metabolic profiles. Participants with hypertriglyceridemia had lower MBP levels than those with normal TG level. MMP levels were not significantly different between the participants with normal and abnormal weight of all metabolic parameters. Participants with hypertriglyceridemia had lower MBP levels than those with normotriglyceridemia. However, it cannot show the correlation between phthalate and metabolic parameters.

Developmental Neurotoxicity of Methamidophos in the Embryo-Larval Stages of Zebrafish.

Methamidophos is a representative organophosphate insecticide. The knowledge of its developmental neurotoxicity is limited, especially for zebrafish in the early stages of their life. Four hour post-fertilization (hpf) zebrafish embryos were exposed to several environmentally relevant concentrations of methamidophos (0, 25, and 500 μg/L) for up to 72 hpf. Locomotor behavior was then studied in the zebrafish larvae at this timepoint. Acridine orange (AO) staining was carried out in the zebrafish larvae, and the mRNA levels of genes associated with neural development (mbp and syn2a) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The number of escape responders for mechanical stimulation was significantly decreased in exposed groups. AO staining showed noticeable signs of apoptosis mainly in the brain. In addition, the mRNA levels of mbp and syn2a were both significantly down-regulated in exposed groups. Our study provides the first evidence that methamidophos exposure can cause developmental neurotoxicity in the early stages of zebrafish life, which may be caused by the effect of methamidophos on neurodevelopmental genes and the activation of cell apoptosis in the brain.

Нейропротекторное действие фенибута и нейроглутама при экспериментальной ишемии головного мозга на фоне измененной иммунореактивности

Изучена церебропротекторная активность фенильных производных гамма-аминомасляной (фенибута) и L-глутаминовой кислоты (нейроглутама) при моделировании ишемии головного мозга (ИГМ) на фоне интактного и измененного иммунитета животных. Исследуемые вещества вводились внутрибрюшинно соответственно в дозах 25 и 26 мг/кг в течение 7 дней после завершения моделирования ИГМ методом поэтапной перевязки общих сонных артерий. Установлено, что супрессия иммунной системы (ИС), вызванная 13-дневным пероральным введением циклоспорина ежедневно в дозе 5 мг/кг, ухудшает течение ИГМ, что проявляется увеличением летальности, более выраженным неврологическим дефицитом, более высоким содержанием в сыворотке крови маркеров повреждения нервной ткани нейронспецифической енолазы (NSE) и основного белка миелина (MBP), снижением мышечной силы, нарушением координации движений, угнетением двигательной и ориентировочно-исследовательской активности по сравнению с животными с ишемией мозга и интактным иммунитетом. ИГМ в условиях стимуляции ИС, вызванной 7-кратным внутрибрюшинным введением липополисахарида (пирогенал, Россия) через день в дозе 10 мкг/кг, вызывала меньшую летальность крыс, а у выживших животных наблюдался меньший неврологический дефицит и более низкие уровни NSE и MBP в сыворотке крови в среднем на 35 % (p ≤ 0,05), более высокие показатели координации движений, мышечной силы и локомоторной активности в среднем на 90 % (p ≤ 0,05). Состояние иммунной системы оказывало значительное влияние на нейропротекторное действие исследуемых веществ при ИГМ. Нейроглутам был эффективен как при интактном иммунитете животных, так и на фоне измененной иммунореактивности. Однако при иммуносупрессии он оказывал максимальный терапевтический эффект при ИГМ, достоверно повышая уровень мозгового кровотока на 56 %, снижая концентрацию NSE и MBP на 57 и 76 % соответственно через 7 дней лечения по сравнению с контрольной группой крыс. Терапевтический потенциал фенибута в большей степени был выражен на фоне активированного иммунитета животных, а при иммуносупрессии его эффективность была низкой.

Akt Regulates Axon Wrapping and Myelin Sheath Thickness in the PNS.

Although the role of the key serine/threonine kinase Akt in promoting CNS myelination has been demonstrated, its role in the PNS has not been established and remains uncertain. This work reveals that Akt controls several key steps of the PNS myelination. First, its activity promotes membrane production and axonal wrapping independent of a transcriptional effect. In myelinated axons, it also enhances myelin thickness through the mTOR pathway. Finally, sustained Akt activation in Schwann cells leads to hypermyelination/dysmyelination, mimicking some features present in neuropathies, such as hereditary neuropathy with liability to pressure palsies or demyelinating forms of Charcot-Marie-Tooth disease. Together, these data demonstrate the role of Akt in regulatory mechanisms underlying axonal wrapping and myelination in the PNS.

Neuroglial alterations in the zebrafish brain exposed to cadmium chloride.

Cadmium is an extremely toxic heavy metal that widely occurs in industrial workplaces with various hazardous effects on brain functions. The cytotoxic effects of cadmium chloride (CdCl2 ) on the neuroglial components of the zebrafish brain were analysed by detecting the glial fibrillary acidic protein (GFAP) expression and the mRNA levels of myelin genes mbp, mpz and plp1 in adult specimens exposed to cadmium for 2, 7 and 16 days. A significant decrease in the GFAP protein by Western blotting experiments was observed after 2 days of treatment, reaching 55% after 16 days. No change was observed in the mRNA levels. Using immunohistochemistry, a reduction in GFAP-positive structures was revealed with a progressive trend in all the brains at 2, 7 and 16 days of treatment. In particular, a considerable reduction in GFAP-positive fibres, with a different course, was observed in the ventricle areas and at the pial surface and in blood vessels after 16 days. Our experiments also showed a structural and chemical alteration of myelin and upregulation of mpz mRNA levels, the oligodendrocyte gene that is upregulated in experiments of neuronal injury, but not of plp1 and mbp mRNA levels, other myelin structural genes. These data confirm the toxic action of cadmium on the zebrafish brain. This action is time-dependent and involves the glial cells, key components of the protection and function of nerve cells, hence the basis for many neurological diseases. Copyright © 2016 John Wiley & Sons, Ltd.

Urinary Phthalate Metabolites in American Alligators (Alligator mississippiensis) from Selected Florida Wetlands.

Phthalates have been shown to cause endocrine disruption in laboratory animals and are associated with altered development of the reproductive system in humans. Further, human have significant exposure to phthalates. However, little is known concerning the exposure of wildlife to phthalates. We report urinary phthalate metabolite concentrations from fifty juvenile alligators from three Florida lakes and a site in the Everglades. Urinary phthalate monoester concentrations varied widely among alligators from the different sites but also among alligators from the same site. Mono-2-ethylhexy phthalate and monobutyl phthalate were found in most samples of alligator urine with maximums of 35,700ng/mL and 193ng/mL, respectively. Monobenzyl phthalate was found in 5 alligators with a maximum of 66.7ng/mL. Other monoesters were found in only one or two alligator urine samples. The wide variation within and among sites, in addition to the high levels of mEHP, mBP and mBzP, is consistent with exposure arising from the intermittent spraying of herbicide formulations to control invasive aquatic plants in Florida freshwater sites. Phthalate diesters are used as adjuvants in many of these formulations.

Early Life Exposure To Phthalate Diesters: Associations With Thyroid Function And Cognitive Function

Background: Epidemiological studies concerning the relations of exposure to phthalates, thyroid function and cognitive function among children could be limited. Objectives: We conducted the longitudinal study to examine the associations of prenatal and postnatal exposure to phthalates, thyroid function and cognitive function in children 2-9 years old. Methods: We recruited 430 pregnant women in their trimester in Taichung, Taiwan from 2001-2002. A total of 110, 79, and 76 children were followed up at ages 2, 5, and 8, respectively. The serum levels of thyroxine (T4), unbound T4 (FT4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), and thyroxine-binding globulin (TBG) in children were measured at three different time points using radioimmunoassay. We also evaluated the children's cognitive function at three followed-up visits using the Bayley and Wechsler tests for assessing neurocognitive function and intelligence (IQ). Urine samples from mothers during pregnancy and from children at each follow-ep visit were analyzed for seven metabolite concentrations of widely used phthalate esters (such as MMP, MEP, MBP, MBzP, MEHP, MEHHP, and MEOHP). We constructed a linear mixed model to examine these associations after adjusted for covariates. Results: We found significant inverse associations between the children's levels of urinary MEHHP, MEOHP, and the sum of the three metabolites of di(2-ethylhexyl) and their serum levels of FT4 (i.e. Beta= -0.04, 95% CI: -0.07, -0.01 for MEOHP). Urinary MMP, MEP, MBP, MBzP, MEHP, and MEOHP levels in children were significantly negatively related to IQ scores (i.e. Beta= -1.85, 95% CI: -3.40, -0.30 for MEOHP). We found a marginally significant positive relationship between the children's serum levels of FT4 and their IQ scores (Beta=5.81, 95% CI: -2.74, 14.36 for MEOHP). Conclusions: Early life exposure to phthalate diesters could be associated with decreasing thyroid function and cognitive development in the young children.