Alcohol Affects the Brain's Resting-State Network in Social Drinkers

Acute alcohol intake is known to enhance inhibition through facilitation of GABAA receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN). To test our hypothesis, electroencephalographic (EEG) measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC) on standardized Low Resolution Electromagnetic Tomography (sLORETA) solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected) in alpha, beta (eyes-open) and theta bands (eyes-closed) following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05). Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo). Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as expected, to increased GABA transmission and functional connectivity, while long-term alcohol consumption may be linked to exactly the opposite effect

Magnesium administration provokes motor unit survival, after sciatic nerve injury in neonatal rats

BACKGROUND: We examined the time course of the functional alterations in two types of muscles following sciatic nerve crush in neonatal rats and the neuroprotective effect of Mg(2+). METHODS: The nerve crush was performed on the 2(nd )postnatal day. MgSO(4)*7H(2)O was administered daily for two weeks. Animals were examined for the contractile properties and for the number of motor units of extensor digitorum longus and soleus muscles at three postnatal stages and adulthood. Four experimental groups were included in this study: i) controls, ii) axotomized rats, iii) magnesium treated controls and iv) axotomized and Mg(2+)-treated rats. RESULTS: Axotomy resulted in 20% MU survival in EDL and 50% in soleus. In contrast, magnesium treatment resulted in a significant motor unit survival (40% survival in EDL and 80% in soleus). The neuroprotective effects of Mg(2+ )were evident immediately after the Mg(2+)-treatment. Immature EDL and soleus muscles were slow and fatigueable. Soleus gradually became fatigue resistant, whereas, after axotomy, soleus remained fatigueable up to adulthood. EDL gradually became fastcontracting. Tetanic contraction in axotomized EDL was just 3,3% of the control side, compared to 15,2% in Mg(2+)-treated adult rats. The same parameter for axotomized soleus was 12% compared to 97% in Mg(2+)-treated adult rats. CONCLUSIONS: These results demonstrate that motoneuron death occurs mostly within two weeks of axotomy. Magnesium administration rescues motoneurons and increases the number of motor units surviving into adulthood. Fast and slow muscles respond differently to axotomy and to subsequent Mg(2+ )treatment in vivo

Efficiency of different decalcification protocols for nasal osseous structures in a rat experimental model of allergic rhinitis, and their effects on epithelial histology: An attempt at standardization

Introduction: Decalcification of osseous specimens is required for histological analysis; this however may cause tissue damage. In rodent models of allergic rhinitis (AR), epithelial histologic assessment necessitates prior decalcification of the nasal osseous structures. However, respiratory epithelium is highly susceptible to damage, and rat nasal architecture is elaborate and its sectioning is challenging. Nevertheless, decalcification is not standardized in experimental AR. We therefore undertook this task, in order to reduce experimental bias. Methods: Six-to-eight week-old Wistar rats underwent an AR protocol. Subsequently, nasal structures were decalcified in the following mediums: (i) formic acid 10% for 5 and 20 days; (ii) formic acid 15% for 5 and 15 days; (iii) Morse Solution for 5 and 20 days and (iv) EDTA for 20 and 40 days. Decalcification efficiency/speed was evaluated via radiographic analysis. Furthermore, specimens were stained with hematoxylin and eosin and assessed for preservation of epithelial features. Results: Specimens were appropriately decalcified in 5 days in the formic acid-based mediums and in 20 days in EDTA with minimal epithelial damage. EDTA for 40 days had no unacceptable adverse effects; conversely, 15 and/or 20 days in acid-based agents provided no extra benefit for decalcification and were detrimental to the epithelium. Conclusions: EDTA treatment for 20 days is appropriate for decalcification of nasal structures in rat models of allergic rhinitis; further incubation preserves epithelial integrity but is not required. When urgency is a factor, formic-acid-based decalcification for 5 days yields acceptable results. © 2014 Elsevier GmbH

Association of brain natriuretic peptide and adrenomedullin plasma levels with left ventricular filling pressures in end-stage renal disease patients on hemodialysis

OBJECTIVE: Adrenomedullin (ADM) and brain natriuretic peptide (BNP) are known to be associated with elevated left ventricular filling pre ssures. However, little is known about this association in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF). Our objective was to evaluate the potential association between E/e&apos; ratio and plasma levels of BNP and ADM in end-stage renal disease (ESRD) patients with preserved LVEF undergoing chronic hemodialysis. PATIENTS AND METHODS: The study group enrolled 62 ESRD patients treated with hemodialysis three times weekly. BNP and ADM plasma concentration measurements and echocardiographic examination were performed 30 minutes after hemodialysis. E/e&apos; ratio, evaluated by Tissue Doppler imaging and measured at the basal septum, was used as a surrogate marker for assessing left ventricular filling pressures. RESULTS: The mean age of patients was 62 ± 25 years. The mean BNP and ADM values after hemodialysis were 0.40 ± 6.73 ng/ml and 0.06 ± 2.12 ng/ml, respectively. Elderly patients with hypertrophied left ventricles and larger left atria displayed high er E/e&apos; value s. BN P (r = 0. 324. p = 0.018) and ADM (r = 0.319, p = 0.042) plasma levels were positively and significantly associated with E/e?. Multivariate regression analysis including BNP, ADM, age, hemodialysis duration, left ventricular end-systolic volume index, LVEF, left ventricular mass index and left atrium volume index, revealed that ADM (p-value 0.025) but not BNP levels, were independently associated with the E/e&apos; ratio. CONCLUSIONS: ADM, but not BNP, was independently associated with septal E/e&apos; in HD patients with preserved LVEF. ADM plasma levels can be used as a surrogate index to assess left ventricular filling pressures in HD patients. © 2018 European Review for Medical and Pharmacological Sciences. All rights reserved

The Effect of Porcine Orexin a on Glucose-Dependent Insulinotropic Polypeptide Plasma Concentrations in Pigs

The orexigenic system was discovered in 1998. It consists of two neuropeptides, Orexin A and Orexin B. Researchers have focused more on Orexin A, since its intracerebroventricular injection into the lateral ventricle of the rat's brain causes an increase in the consumption of food. Besides, it seems that, apart from appetite, Orexin A regulates many other physiological functions with unknown regulatory and metabolic mechanisms. Orexin A is produced by a small group of neurons located in and around the lateral hypothalamic area. It has been known for decades that the latter is involved in regulating feeding in mammals. An intravenous injection of Orexin A causes changes in insulin and glucagon plasma concentrations in rats. In this study, we investigated the possible effects of the central administration of porcine Orexin A on glucose-dependent insulinotropic polypeptide plasma concentrations in pigs, and examined whether these changes are related to the possible effect of the neuropeptide on the enteroinsular axis

The effect of inebriation on human brain functional connectivity

Given the effect of acute alcohol intake on the human emotional state, we hypothesized that even a moderate dose of alcohol will affect the brain activity of social drinkers, both at rest (default-mode network, DMN) and when passively viewing emotional stimuli, in terms of functional connectivity. Electroencephalographic (EEG) recordings were performed on 27 participants after receiving an alcoholic beverage and placebo respectively, at rest and during passive viewing of affective images from the International Affective Picture System (IAPS). The selected images were representative of 4 categories: pleasant and high arousing, pleasant and low arousing, unpleasant and high arousing and unpleasant and low arousing. Salivary alcohol served to measure the inebriation levels. The activity of cortical sources was estimated with the standardized Low Resolution Electromagnetic Tomography (sLORETA). The magnitude square coherence (MSC) on each pair of them was estimated for each frequency band to form functional networks among the cortical sources. The networks were treated in the context of graph theory and their global parameters were calculated. Our preliminary results refer to the DMN connectivity. The MSC averaged across all sources' pairs, along with the global efficiency of the DMN, were significantly (p < 0.05) higher following alcohol intake (vs. placebo) in alpha and beta bands. The inter-connectivity of certain nodes, roughly outlining the DMN, was elevated (p < .05 corrected) in alpha band during alcohol sessions indicating a pronounced baseline functional connectivity. Our findings support the hypothesis that alcohol affects the functional connectivity of the DMN not necessarily locally, but in a more global way. A resting state pronounced functional connectivity in the human brain can elucidate to an extent the attention impairment already observed following acute alcohol intake, since the transition to an attentive state would be more demanding. Extensive functional connectivity analysis is underway in order to examine the effect of acute alcohol intake on the connectivity patterns eliciting during passive viewing of emotional stimuli examining whether it is different for different kinds of affective images. As expected, measures that globally quantify the brain functional connectivity were sensitively affected by alcohol-induced alterations in the DMN. We will soon have some findings on the functional networks formed as a response to emotional stimuli following inebriation

Significant alcohol effect on graph parameters across different thresholds.

<p>Double stars (**) indicate significant p-values (p<0.03), single stars (*) indicate marginally significant effects (p<0.06). To maintain the high resolution and quality of the figures, we did not include all the results for the many different thresholds, but only for the first seven. Characteristic path length, clustering coefficient, and consequently small-worldness are normalized by random surrogate graphs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048641#pone.0048641-Welch1" target="_blank">[49]</a>.</p

Alcohol-induced significant connectivity differences.

<p>Differences during eyes-open and during eyes-closed sessions are presented in the upper and lower panel respectively. Significantly (p<.05, FDR corrected) increased connectivity is shown in the upper rows (red connections), decreased in the lower rows (blue connections). The number of significantly affected connections is also presented for each frequency band.</p