The Role of Tenascin-C on the Structural Plasticity of Perineuronal Nets and Synaptic Expression in the Hippocampus of Male Mice.

Neuronal plasticity is a crucial mechanism for an adapting nervous system to change. It is shown to be regulated by perineuronal nets (PNNs), the condensed forms of the extracellular matrix (ECM) around neuronal bodies. By assessing the changes in the number, intensity, and structure of PNNs, the ultrastructure of the PNN mesh, and the expression of inhibitory and excitatory synaptic inputs on these neurons, we aimed to clarify the role of an ECM glycoprotein, tenascin-C (TnC), in the dorsal hippocampus. To enhance neuronal plasticity, TnC-deficient (TnC-/-) and wild-type (TnC+/+) young adult male mice were reared in an enriched environment (EE) for 8 weeks. Deletion of TnC in TnC-/- mice showed an ultrastructural reduction of the PNN mesh and an increased inhibitory input in the dentate gyrus (DG), and an increase in the number of PNNs with a rise in the inhibitory input in the CA2 region. EE induced an increased inhibitory input in the CA2, CA3, and DG regions; in DG, the change was also followed by an increased intensity of PNNs. No changes in PNNs or synaptic expression were found in the CA1 region. We conclude that the DG and CA2 regions emerged as focal points of alterations in PNNs and synaptogenesis with EE as mediated by TnC.

The impact of early life maternal deprivation on the perineuronal nets in the prefrontal cortex and hippocampus of young adult rats.

Early life stress negatively impacts brain development and affects structure and function of parvalbumin immunopositive (PV+) inhibitory neurons. Main regulators of PV+ interneurons activity and plasticity are perineuronal nets (PNNs), an extracellular matrix formation that enwraps PV+ interneurons mainly in the neocortex and hippocampus. To experimentally address the impact of early life stress on the PNNs and PV+ interneurons in the medial prefrontal cortex and dorsal hippocampus in rats, we employed a 24 h maternal deprivation protocol. We show that maternal deprivation in the medial prefrontal cortex of adult rats caused a decrease in density of overall PNNs and PNNs that enwrap PV+ interneurons in the rostral cingulate cortex. Furthermore, a staining intensity decrease of overall PNNs and PNN+/PV+ cells was found in the prelimbic cortex. Finally, a decrease in both intensity and density of overall PNNs and PNNs surrounding PV+ cells was observed in the infralimbic cortex, together with increase in the intensity of VGAT inhibitory puncta. Surprisingly, maternal deprivation did not cause any changes in the density of PV+ interneurons in the mPFC, neither had it affected PNNs and PV+ interneurons in the hippocampus. Taken together, our findings indicate that PNNs, specifically the ones enwrapping PV+ interneurons in the medial prefrontal cortex, are affected by early life stress.

Energy Drinks and Sleep among Adolescents.

Many adolescents worldwide have the problem of meeting recommended nightly sleep hours. The causes of sleep disturbance are multifactorial, but interest in food's effect on sleep has dramatically increased lately. In this study, we investigated the association between regular energy drink (ED) intake (weekly or more frequent) and sufficient sleep (SS) (≥8 h) in adolescents. Additional objectives were to examine the relationship between health-related behaviors and SS, stratified by gender. A population-based cross-sectional study was conducted during the 2019/2020 school year from 12 schools in Belgrade. There were 1287 students aged 15 to 19 who participated (37.4% male). We used a modified version of the food frequency questionnaire adapted for Serbian adolescents. Logistic regression revealed that regular ED consumption was an independent risk factor negatively related to SS in both sexes. Additionally, daily vegetable and water intake (≥2 L) showed a positive correlation with SS in boys, while in girls, the odds of realizing SS decreased with statements of sedative use. In conclusion, we show that ED intake is negatively associated with SS in both sexes; daily vegetable and water intake (≥2 L) may raise the odds of SS in boys, while sedative use may decrease the chances of SS in girls.

Structural and Functional Modulation of Perineuronal Nets: In Search of Important Players with Highlight on Tenascins.

The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis.

Serum magnesium level in the first trimester of pregnancy as a predictor of pre-eclampsia - a pilot study.

OBJECTIVES: The aim of this study was to evaluate the importance of serum concentration of magnesium (Mg) in the first trimester of pregnancy for predicting pre-eclampsia (PE). METHODS: This prospective study included 403 pregnant women over 18, with singleton pregnancy (from 11 to 14 weeks of pregnancy). The subjects were divided into a group who subsequently developed PE (PEKT) (n = 61), and a group of healthy pregnancies with no complications and with normal outcomes (TNT) (n = 342). In the first trimester, urea, creatinine, uric acid, Mg, free beta subunit of human chorionic gonadotrophin, plasma protein A related to pregnancy, and C-reactive protein were determined. We followed all subjects until the end of pregnancy. RESULTS: Serum Mg is significantly lower in PEKT than in TNT group (p < 0.001). The serum first trimester Mg level cutoff at ≤0.81 mmol/L had a sensitivity of 77.0% and specificity of 71.6% for the detection of women with PEKT. The level of serum Mg has the strongest significant positive correlation (p < 0.05) with the week of gestational outcomes (R = 0.442), weight (R = 0.416), and Apgar score (R = 0.343) of the newborns, and the strongest significant negative correlation with the number of miscarriages (R = -0.413), serum creatinine (R = -0.471), and the number of pregnancies (R = -0.326). The week of gestational outcome is predicted with the greatest reliability by the serum Mg. CONCLUSIONS: Serum Mg level during the first trimester of pregnancy is a significant prediction tool for PE and could also play an important role in predicting the week of gestational outcome and birth weight of newborns.

Early pregnancy angiogenic proteins levels and pregnancy related hypertensive disorders.

INTRODUCTION: Normal placental vascular development depends on multiple interactions of many regulatory molecules including pro and antiangiogenic proteins. It is considered that these vascular modulators might be one of the factors responsible for development hypertensive disorders in pregnancy. OBJECTIVE: To evaluate and compare the early pregnancy (11-14 week of gestation) serum level of angiogenic proteins sFlt1, VEGF i PIGF between different types of pregnancy related hypertensive disorders. MATERIALS AND METHODS: The study included 177 pregnant women between 11 and 14 weeks of gestation, divided into four study subgroups (preeclampsia group-41, gestational hypertension group-31, chronic hypertension group-32 and miscarriage group-19) and control group-54. Blood samples (serum) were taken for measuring sFlt1, VEGF i PIGF by a quantitative ELISA technique and measuring other biochemical and hematological parameters. RESULTS: Significantly higher levels of sFlt1 were in the subgroups with preeclampsia and miscarriages, significantly lower level of VEGF in the all study subgroups and lover level of PIGF were in miscarriage group. In the groups with chronic and gestational hypertension there were higher level of sFlt1 and lover level of VEGF than in the control group, but the differences did not reach statistical significance. CONCLUSION: Early pregnancy imbalance between antiangiogenic protein sFlt1 and proangiogenic molecules VEGF and PIGF could have impact on pathophysiology of placental disorders which leads to development of pregnancy related hypertensive disorders.

Ceruloplasmin and antioxidative enzymes in pre-eclampsia.

OBJECTIVE: To evaluate diagnostic value of ceruloplasmin together with other enzymatic and nonenzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and uric acid) and to evaluate the level of oxidative stress in patients with pre-eclampsia (PE) and compare it with normal pregnancy. METHODS: In this prospective study, antioxidative markers were investigated in two groups of pregnant women: patients with pre-eclampsia (n = 32) and the healthy pregnant women (n = 60). The following antioxidative markers and enzymes were evaluated: serum ceruloplasmin levels, uric acid, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RESULTS: Serum levels of ceruloplasmin, uric acid and SOD were significantly higher in the PE group compared to the control group. Serum levels of GSH-Px were not significantly higher in the PE group compared to the control group. Serum ceruloplasmin and serum uric acid have the best diagnostic accuracy for oxidative stress in PE and are more accurate compared to antioxidative enzymes -SOD and specially more accurate than GSH-Px. CONCLUSIONS: Serum ceruloplasmin level may have significant role as the markers of oxidative stress in pre-eclampsia especially when used in combination with uric acid levels.

The influence of bacterial vaginosis on gestational week of the completion of delivery and biochemical markers of inflammation in the serum.

BACKGROUND/AIM: Preterm delivery is one of the most common complications in pregnancy, and it is the major cause (75-80%) of all neonatal deaths. Bacterial vaginosis predisposes to an increased risk of preterm delivery, premature rupture of membrane and miscarriage. In this syndrome normal vaginal lactobacilli, which produce protective H2O2, are reduced and replaced with anaerobic, gram-negative bacteria and others. The aim of this study was to evaluate the influence of bacterial vaginosis on the week of delivery and biochemical markers of inflammation in the serum. METHODS: A total of 186 pregnant women were included into this study, between the week 16 and 19 of pregnancy. In the study group there were 76 pregnant women with diagnosed bacterial vaginosis by the criteria based on vaginal Gram-stain Nugent score and Amsel criteria. In the control group there were 110 healthy women with normal vaginal flora. Ultrasound examination was performed in both groups. Vaginal fluid and blood samples were taken to determine biochemical markers with colorimetric methods. RESULTS: The week of delivery was statistically significantly shorter in the study group and the levels of biochemical markers of inflammation (C-reactive protein and fibrinogen in the serum) were statistically significantly higher in women with bacterial vaginosis comparing to the control group. Also the levels of uric acid and white blood cells in the serum were higher in the study group compared to the control one. CONCLUSION: Our study indicates that the pregnancy complicated with bacterial vaginosis ends much earlier than the pregnancy without it. Also, higher levels of biochemical markers of inflammation in the serum in the study group, similarly to results of other studies, suggest that pathophysiological processes responsible for preterm delivery can begin very early in pregnancy.

The effect of angiotensin converting enzyme inhibition on effective renal plasma flow in patients with diffuse renal parenchymal diseases and hypertension.

INTRODUCTION: Angiotensin converting enzyme inhibitors are commonly used to treat various hypertensive conditions and in addition to lowering blood pressure these drugs affect the local renal hemodynamic status, thereby influencing the glomerular filtration rate and effective renal plasma flow. The study was aimed at determining whether angiotensin converting enzyme inhibitors can produce significant changes in effective renal plasma flow in patients with parenchymal renal disease and to assess whether the changes depend on the pre-existing functional status of the kidney. MATERIAL AND METHODS: The study included 80 subjects, 40 subjects with hypertension associated with diffuse renal parenchymal disease and 40 subjects with essential hypertension. All study subjects underwent the baseline effective renal plasma flow measurement and the repeated effective renal plasma flow measurement after administration of captopril. Effective renal plasma flow was determined by 131 I-hippuran clearance in blood samples taken at 20 and 30 minutes. RESULTS: Angiotensin converting enzyme inhibitors caused significant effective renal plasma flow changes in 55% of subjects with diffuse renal parenchymal disease and in 75% of subjects with essential hypertension. The effective renal plasma flow changes were more significant in subjects with preserved renal function (normal baseline effective renal plasma flow) compared to subjects with reduced baseline effective renal plasma flow. CONCLUSION: The application of angiotensin converting enzyme inhibitors in patients with diffuse renal parenchymal disease and in individuals with essential hypertension may result in significant hemodynamic changes in the kidney, accompanied by changes in effective renal plasma flow. The extent of the changes caused by angiotensin converting enzyme inhibitors depends on the preexisting functional status of the kidney.

[Polyostotic Paget's disease of bone: diagnostic dilemma in detection of bone metastases from prostate cancer].

INTRODUCTION: Paget's disease of bone (osteitis deformans) is a rare metabolic disorder of bone remodeling with complex etiology. In the most cases, it is detected by coincidence, during nuclear medicine and radiological diagnostic procedures. Herein we report a case of advanced prostate cancer coexisting with asymptomatic Paget's disease. CASE REPORT: We present a 69-year-old patient, with biochemical recurrence two years after radical prostatectomy for localized prostate cancer and period of stable remission. During the evaluation of metastatic spread of prostate cancer, the bone scintigraphy with technetium diphosphonate showed diffuse areas of increased radiotracer uptake in the left leg long bones and focal changes in the axial part of the skeleton. Scintigraphic findings led to a differential diagnostic dilemma regarding etiology of bone changes, so it was supplemented by standard radiologic methods and laboratory evaluation of bone metabolism parameters. The existence of asymptomatic polyostotic Paget's disease and metastatic bone changes was found at the same time. CONCLUSION: Metastatic bone lesions, in this case from prostate cancer, and asymptomatic Paget's disease may closely resemble each other. They both need careful evaluation in order to determine the proper stages of malignant disease and selection of appropriate therapies for patients.