Nurturing development: how a mother's nutrition shapes offspring's brain through the gut.

Pregnancy is a transformative period marked by profound physical and emotional changes, with far-reaching consequences for both mother and child. Emerging research has illustrated the pivotal role of a mother's diet during pregnancy in influencing the prenatal gut microbiome and subsequently shaping the neurodevelopment of her offspring. The intricate interplay between maternal gut health, nutrition, and neurodevelopmental outcomes has emerged as a captivating field of investigation within developmental science. Acting as a dynamic bridge between mother and fetus, the maternal gut microbiome, directly and indirectly, impacts the offspring's neurodevelopment through diverse pathways. This comprehensive review delves into a spectrum of studies, clarifying putative mechanisms through which maternal nutrition, by modulating the gut microbiota, orchestrates the early stages of brain development. Drawing insights from animal models and human cohorts, this work underscores the profound implications of maternal gut health for neurodevelopmental trajectories and offers a glimpse into the formulation of targeted interventions able to optimize the health of both mother and offspring. The prospect of tailored dietary recommendations for expectant mothers emerges as a promising and accessible intervention to foster the growth of beneficial gut bacteria, potentially leading to enhanced cognitive outcomes and reduced risks of neurodevelopmental disorders.

Towards an electroencephalographic measure of awareness based on the reactivity of oscillatory macrostates to hearing a subject's own name.

We proposed that the brain's electrical activity is composed of a sequence of alternating states with repeating topographic spectral distributions on scalp electroencephalogram (EEG), referred to as oscillatory macrostates. The macrostate showing the largest decrease in the probability of occurrence, measured as a percentage (reactivity), during sensory stimulation was labelled as the default EEG macrostate (DEM). This study aimed to assess the influence of awareness on DEM reactivity (DER). We included 11 middle cerebral artery ischaemic stroke patients with impaired awareness having a median Glasgow Coma Scale (GCS) of 6/15 and a group of 11 matched healthy controls. EEG recordings were carried out during auditory 1 min stimulation epochs repeating either the subject's own name (SON) or the SON in reverse (rSON). The DEM was identified across three SON epochs alternating with three rSON epochs. Compared with the patients, the DEM of controls contained more posterior theta activity reflecting source dipoles that could be mapped in the posterior cingulate cortex. The DER was measured from the 1 min quiet baseline preceding each stimulation epoch. The difference in mean DER between the SON and rSON epochs was measured by the salient EEG reactivity (SER) theoretically ranging from -100% to 100%. The SER was 12.4 ± 2.7% (Mean ± standard error of the mean) in controls and only 1.3 ± 1.9% in the patient group (P < 0.01). The patient SER decreased with the Glasgow Coma Scale. Our data suggest that awareness increases DER to SON as measured by SER.

Increasing Value and Reducing Waste of Research on Neurofeedback Effects in Post-traumatic Stress Disorder: A State-of-the-Art-Review.

Post-Traumatic Stress Disorder (PTSD) is often considered challenging to treat due to factors that contribute to its complexity. In the last decade, more attention has been paid to non-pharmacological or non-psychological therapies for PTSD, including neurofeedback (NFB). NFB is a promising non-invasive technique targeting specific brainwave patterns associated with psychiatric symptomatology. By learning to regulate brain activity in a closed-loop paradigm, individuals can improve their functionality while reducing symptom severity. However, owing to its lax regulation and heterogeneous legal status across different countries, the degree to which it has scientific support as a psychiatric treatment remains controversial. In this state-of-the-art review, we searched PubMed, Cochrane Central, Web of Science, Scopus, and MEDLINE and identified meta-analyses and systematic reviews exploring the efficacy of NFB for PTSD. We included seven systematic reviews, out of which three included meta-analyses (32 studies and 669 participants) that targeted NFB as an intervention while addressing a single condition-PTSD. We used the MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 and the criteria described by Cristea and Naudet (Behav Res Therapy 123:103479, 2019, https://doi.org/10.1016/j.brat.2019.103479 ) to identify sources of research waste and increasing value in biomedical research. The seven assessed reviews had an overall extremely poor quality score (5 critically low, one low, one moderate, and none high) and multiple sources of waste while opening opportunities for increasing value in the NFB literature. Our research shows that it remains unclear whether NFB training is significantly beneficial in treating PTSD. The quality of the investigated literature is low and maintains a persistent uncertainty over numerous points, which are highly important for deciding whether an intervention has clinical efficacy. Just as importantly, none of the reviews we appraised explored the statistical power, referred to open data of the included studies, or adjusted their pooled effect sizes for publication bias and risk of bias. Based on the obtained results, we identified some recurrent sources of waste (such as a lack of research decisions based on sound questions or using an appropriate methodology in a fully transparent, unbiased, and useable manner) and proposed some directions for increasing value (homogeneity and consensus) in designing and reporting research on NFB interventions in PTSD.

Functional Enhancement and Characterization of an Electrophysiological Mapping Electrode Probe with Carbonic, Directional Macrocontacts.

Electrophysiological mapping (EM) using acute electrode probes is a common procedure performed during functional neurosurgery. Due to their constructive specificities, the EM probes are lagging in innovative enhancements. This work addressed complementing a clinically employed EM probe with carbonic and circumferentially segmented macrocontacts that are operable both for neurophysiological sensing ("recording") of local field potentials (LFP) and for test stimulation. This paper illustrates in-depth the development that is based on the direct writing of functional materials. The unconventional fabrication processes were optimized on planar geometry and then transferred to the cylindrically thin probe body. We report and discuss the constructive concept and architecture of the probe, characteristics of the electrochemical interface deduced from voltammetry and chronopotentiometry, and the results of in vitro and in vivo recording and pulse stimulation tests. Two- and three-directional macrocontacts were added on probes having shanks of 550 and 770 µm diameters and 10-23 cm lengths. The graphitic material presents a ~2.7 V wide, almost symmetric water electrolysis window, and an ultra-capacitive charge transfer. When tested with clinically relevant 150 µs biphasic current pulses, the interfacial polarization stayed safely away from the water window for pulse amplitudes up to 9 mA (135 µC/cm2). The in vivo experiments on adult rat models confirmed the high-quality sensing of LFPs. Additionally, the in vivo-prevailing increase in the electrode impedance and overpotential are discussed and modeled by an ionic mobility-reducing spongiform structure; this restricted diffusion model gives new applicative insight into the in vivo-uprisen stimulation overpotential.

Melatonin-Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions.

Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin's most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community-namely, the gut microbiota, in multiple critical functions of the organism- has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.

Neurological Manifestations of SARS-CoV2 Infection: A Narrative Review.

The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

Near-Infrared Spectroscopy Usefulness in Validation of Hyperventilation Test.

Background: The hyperventilation test is used in clinical practice for diagnosis and therapeutic purposes; however, in the absence of a standardized protocol, the procedure varies significantly, predisposing tested subjects to risks such as cerebral hypoxia and ischemia. Near-infrared spectroscopy (NIRS), a noninvasive technique performed for cerebral oximetry monitoring, was used in the present study to identify the minimum decrease in the end-tidal CO2 (ETCO2) during hyperventilation necessary to induce changes on NIRS. Materials and Methods: We recruited 46 volunteers with no preexisting medical conditions. Each subject was asked to breathe at a baseline rate (8−14 breaths/min) for 2 min and then to hyperventilate at a double respiratory rate for the next 4 min. The parameters recorded during the procedure were the regional cerebral oxyhemoglobin and deoxyhemoglobin concentrations via NIRS, ETCO2, and the respiratory rate. Results: During hyperventilation, ETCO2 values dropped (31.4 ± 12.2%) vs. baseline in all subjects. Changes in cerebral oximetry were observed only in those subjects (n = 30) who registered a decrease (%) in ETCO2 of 37.58 ± 10.34%, but not in the subjects (n = 16) for which the decrease in ETCO2 was 20.31 ± 5.6%. According to AUC-ROC analysis, a cutoff value of ETCO2 decrease >26% was found to predict changes in oximetry (AUC-ROC = 0.93, p < 0.0001). Seven subjects reported symptoms, such as dizziness, vertigo, and numbness, throughout the procedure. Conclusions: The rise in the respiratory rate alone cannot effectively predict the occurrence of a cerebral vasoconstrictor response induced by hyperventilation, and synchronous ETCO2 and cerebral oximetry monitoring could be used to validate this clinical test. NIRS seems to be a useful tool in predicting vasoconstriction following hyperventilation.

Does a Single Exposure to General Anesthesia Have a Cumulative Effect on the Developing Brain after Mild Perinatal Asphyxia?

BACKGROUND: General anesthesia (GA) in pediatric patients represents a clinical routine. Factors such as increased birth age and maternal chronic conditions cause more infants to experience hypoxic-ischemic encephalopathy, an additional risk for anesthesia. AIM: This study evaluates the effect of one sevoflurane-induced GA episode on the immature brain previously exposed to perinatal asphyxia (PA). METHODS: Postnatal day 6 (PND6) Wistar rats were exposed to a 90-min episode of normoxia/PA and at PND15 to a 120-min episode of normoxia/GA. Four groups were analyzed: Control (C), PA, GA, and PA-GA. Post-exposures, fifteen pups/group were sacrificed and the hippocampi were isolated to assess S-100B and IL-1B protein levels, using ELISA. At maturity, the behavior was assessed by: forced swimming test (FST), and novel object recognition test. RESULTS: Hippocampal S-100B level was increased in PA, GA, and PA-GA groups, while IL-1B was increased in PA, but decreased in PA-GA. The immobility time was increased in PA and PA-GA, in FST. CONCLUSIONS: Both PA and GA contribute to glial activation, however with no cumulative effect. Moreover, PA reduces the rats' mobility, irrespective of GA exposure, while memory evaluated by the novel object recognition test was not influenced.

Oxytocin and vasopressin in the hippocampus.

Oxytocin (OXT) and vasopressin (AVP) are related neuropeptides that exert a wide range of effects on general health, homeostasis, development, reproduction, adaptability, cognition, social and nonsocial behaviors. The two peptides are mainly of hypothalamic origin and execute their peripheral and central physiological roles via OXT and AVP receptors, which are members of the G protein-coupled receptor family. These receptors, largely distributed in the body, are abundantly expressed in the hippocampus, a brain region particularly vulnerable to stress exposure and various lesions. OXT and AVP have important roles in the hippocampus, by modulating important processes like neuronal excitability, network oscillatory activity, synaptic plasticity, and social recognition memory. This chapter includes an overview regarding OXT and AVP structure, synthesis, receptor distribution, and functions, focusing on their relationship with the hippocampus and mechanisms by which they influence hippocampal activity. Brief information regarding hippocampal structure and susceptibility to lesions is also provided. The roles of OXT and AVP in neurodevelopment and adult central nervous system function and disorders are highlighted, discussing their potential use as targeted therapeutic tools in neuropsychiatric diseases.

A method to assess the default EEG macrostate and its reactivity to stimulation.

OBJECTIVE: The default mode network (DMN) is deactivated by stimulation. We aimed to assess the DMN reactivity impairment by routine EEG recordings in stroke patients with impaired consciousness. METHODS: Binocular light flashes were delivered at 1 Hz in 1-minute epochs, following a 1-minute baseline (PRE). The EEG was decomposed in a series of binary oscillatory macrostates by topographic spectral clustering. The most deactivated macrostate was labeled the default EEG macrostate (DEM). Its reactivity (DER) was quantified as the decrease in DEM occurrence probability during stimulation. A normalized DER index (DERI) was calculated as DER/PRE. The measures were compared between 14 healthy controls and 32 comatose patients under EEG monitoring following an acute stroke. RESULTS: The DEM was mapped to the posterior DMN hubs. In the patients, these DEM source dipoles were 3-4 times less frequent and were associated with an increased theta activity. Even in a reduced 6-channel montage, a DER below 6.26% corresponding to a DERI below 0.25 could discriminate the patients with sensitivity and specificity well above 80%. CONCLUSION: The method detected the DMN impairment in post-stroke coma patients. SIGNIFICANCE: The DEM and its reactivity to stimulation could be useful to monitor the DMN function at bedside.

Maternal Citicoline-Supplemented Diet Improves the Response of the Immature Hippocampus to Perinatal Asphyxia in Rats.

BACKGROUND: Citicoline represents a dietary source of choline, an essential nutrient, and precursor of cell membrane components, highly required during development and post-injury recovery. OBJECTIVES: We previously showed that perinatal asphyxia (PA) induces hippocampal neuroinflammation and injury that are subject to epigenetic change by maternal diet. The present study investigates maternal citicoline-supplemented diet (CSD) impact on offspring hippocampal response to PA. METHODS: Six-day-old Wistar rats from mothers with standard-diet or CSD were exposed to PA. The hippocampal inflammation and injury were assessed by interleukin-1 beta (IL-1b), tumor necrosis factor-alpha (TNFα), and S-100B protein (S-100B), 24-48 h post-asphyxia. The microRNAs species miR124, miR132, miR134, miR146, and miR15a were measured from the hippocampus 24 h post-asphyxia, to investigate its epigenetic response to PA and maternal diet. At maturity, the offspring's behavior was analyzed using open field (OFT), T-maze (TMT), and forced swimming (FST) tests. RESULTS: Our data show that the maternal CSD decreased IL-1b (p = 0.02), TNFα (p = 0.007), and S100B (p = 0.01) at 24 h postexposure, upregulated miR124 (p = 0.03), downregulated miR132 (p = 0.002) and miR134 (p = 0.001), shortened the immobility period in FST (p = 0.01), and increased the percentage of passed trials in TMT (p = 0.01) compared to standard-diet. CONCLUSIONS: Maternal CSD reduces hippocampal inflammation and S100B level, triggers epigenetic changes related to homeostatic synaptic plasticity, memory formation, and neuronal tolerance to asphyxia, decreases the depressive-like behavior, and improves the lucrative memory in offspring subjected to PA. Thus, citicoline could be valuable as a maternal dietary strategy in improving the brain response to PA.

Capsaicin and Gut Microbiota in Health and Disease.

Capsaicin is a widespread spice known for its analgesic qualities. Although a comprehensive body of evidence suggests pleiotropic benefits of capsaicin, including anti-inflammatory, antioxidant, anti-proliferative, metabolic, or cardioprotective effects, it is frequently avoided due to reported digestive side-effects. As the gut bacterial profile is strongly linked to diet and capsaicin displays modulatory effects on gut microbiota, a new hypothesis has recently emerged about its possible applicability against widespread pathologies, such as metabolic and inflammatory diseases. The present review explores the capsaicin-microbiota crosstalk and capsaicin effect on dysbiosis, and illustrates the intimate mechanisms that underlie its action in preventing the onset or development of pathologies like obesity, diabetes, or inflammatory bowel diseases. A possible antimicrobial property of capsaicin, mediated by the beneficial alteration of microbiota, is also discussed. However, as data are coming mostly from experimental models, caution is needed in translating these findings to humans.

Reduced Interhemispheric Coherence after Cerebellar Vermis Output Perturbation.

Motor coordination and motor learning are well-known roles of the cerebellum. Recent evidence also supports the contribution of the cerebellum to the oscillatory activity of brain networks involved in a wide range of disorders. Kainate, a potent analog of the excitatory neurotransmitter glutamate, can be used to induce dystonia, a neurological movement disorder syndrome consisting of sustained or repetitive involuntary muscle contractions, when applied on the surface of the cerebellum. This research aims to study the interhemispheric cortical communication between the primary motor cortices after repeated kainate application on cerebellar vermis for five consecutive days, in mice. We recorded left and right primary motor cortices electrocorticograms and neck muscle electromyograms, and quantified the motor behavior abnormalities. The results indicated a reduced coherence between left and right motor cortices in low-frequency bands. In addition, we observed a phenomenon of long-lasting adaptation with a modification of the baseline interhemispheric coherence. Our research provides evidence that the cerebellum can control the flow of information along the cerebello-thalamo-cortical neural pathways and can influence interhemispheric communication. This phenomenon could function as a compensatory mechanism for impaired regional networks.

Melatonin's Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease.

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

A Broader Perspective on Anti-Ro Antibodies and Their Fetal Consequences-A Case Report and Literature Review.

The presence of maternal Anti-Ro/Anti-La antibodies causes a passively acquired autoimmunity that may be associated with serious fetal complications. The classic example is the autoimmune-mediated congenital heart block (CHB) which is due in most cases to the transplacental passage of Anti-Ro/Anti-La antibodies. The exact mechanisms through which these pathologic events arise are linked to disturbances in calcium channels function, impairment of calcium homeostasis and ultimately apoptosis, inflammation and fibrosis. CHB still represents a challenging diagnosis and a source of debate regarding the best management. As the third-degree block is usually irreversible, the best strategy is risk awareness and prevention. Although CHB is a rare occurrence, it affects one in 20,000 live births, with a high overall mortality rate (up to 20%, with 70% of in utero deaths). There is also concern over the lifelong consequences, as most babies need a pacemaker. This review aims to offer, apart from the data needed for a better understanding of the issue at hand, a broader perspective of the specialists directly involved in managing this pathology: the rheumatologist, the maternal-fetal specialist and the cardiologist. To better illustrate the theoretical facts presented, we also include a representative clinical case.

Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System.

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as high as 10 cases per 1000 live births in the less developed countries, prompts the need for better awareness and prevention of cases at risk, together with management by easily applicable protocols. PA acts first and foremost on the nervous tissue, but also on the heart, by hypoxia and subsequent ischemia-reperfusion injury. Myocardial development at birth is still incomplete and cannot adequately respond to this aggression. Cardiac dysfunction, including low ventricular output, bradycardia, and pulmonary hypertension, complicates the already compromised circulatory status of the newborn with PA. Multiorgan and especially cardiovascular failure seem to play a crucial role in the secondary phase of hypoxic-ischemic encephalopathy (HIE) and its high mortality rate. Hypothermia is an acceptable solution for HIE, but there is a fragile equilibrium between therapeutic gain and cardiovascular instability. A profound understanding of the underlying mechanisms of the nervous and cardiovascular systems and a close collaboration between the bench and bedside specialists in these domains is compulsory. More resources need to be directed toward the prevention of PA and the consecutive decrease of cardiovascular dysfunction. Not much can be done in case of an unexpected acute event that produces PA, where recognition and prompt delivery are the key factors for a positive clinical result. However, the situation is different for high-risk pregnancies or circumstances that make the fetus more vulnerable to asphyxia. Improving the outcome in these cases is possible through careful monitoring, identifying the high-risk pregnancies, and the implementation of novel prenatal strategies. Also, apart from adequately supporting the heart through the acute episode, there is a need for protocols for long-term cardiovascular follow-up. This will increase our recognition of any lasting myocardial damage and will enhance our perspective on the real impact of PA. The goal of this article is to review data on the cardiovascular consequences of PA, in the context of an immature cardiovascular system, discuss the potential contribution of cardiovascular impairment on short and long-term outcomes, and propose further directions of research in this field.

Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation.

Neuronal ischemia results in chloride gradient alterations which impact the excitatory-inhibitory balance, volume regulation, and neuronal survival. Thus, the Na+/K+/Cl- co-transporter (NKCC1), the K+/ Cl- co-transporter (KCC2), and the gamma-aminobutyric acid A (GABAA) receptor may represent therapeutic targets in stroke, but a time-dependent effect on neuronal viability could influence the outcome. We, therefore, successively blocked NKCC1, KCC2, and GABAA (with bumetanide, DIOA, and gabazine, respectively) or activated GABAA (with isoguvacine) either during or after oxygen-glucose deprivation (OGD). Primary hippocampal cultures were exposed to a 2-h OGD or sham normoxia treatment, and viability was determined using the resazurin assay. Neuronal viability was significantly reduced after OGD, and was further decreased by DIOA treatment applied during OGD (p < 0.01) and by gabazine applied after OGD (p < 0.05). Bumetanide treatment during OGD increased viability (p < 0.05), while isoguvacine applied either during or after OGD did not influence viability. Our data suggests that NKCC1 and KCC2 function has an important impact on neuronal viability during the acute ischemic episode, while the GABAA receptor plays a role during the subsequent recovery period. These findings suggest that pharmacological modulation of transmembrane chloride transport could be a promising approach during stroke and highlight the importance of the timing of treatment application in relation to ischemia-reoxygenation.

Electrical Stimulation in the Claustrum Area Induces a Deepening of Isoflurane Anesthesia in Rat.

The role of the claustrum in consciousness and vigilance states was proposed more than two decades ago; however, its role in anesthesia is not yet understood, and this requires more investigation. The aim of our study was to assess the impact of claustrum electrical stimulation during isoflurane anesthesia in adult rats. The claustrum in the left hemisphere was electrically stimulated using a bipolar tungsten electrode inserted stereotaxically. In order to monitor the anesthetic depth, the electrocorticogram (ECoG) was recorded before, during, and after claustrum stimulation using frontal and parietal epidural electrodes placed over the left hemisphere. After reaching stabilized slow-wave isoflurane anesthesia, twenty stimuli, each of one second duration with ten seconds interstimulus duration, were applied. ECoG analysis has shown that, after a delay from the beginning of stimulation, the slow-wave ECoG signal changed to a transient burst suppression (BS) pattern. Our results show that electrical stimulation of the claustrum area during slow-wave isoflurane anesthesia induces a transitory increase in anesthetic depth, documented by the appearance of a BS ECoG pattern, and suggests a potential role of claustrum in anesthesia.

Lipid Profile Changes Induced by Chronic Administration of Anabolic Androgenic Steroids and Taurine in Rats.

Background and Objectives: Anabolic androgenic steroids (AAS), used as a therapy in various diseases and abused in sports, are atherogenic in supraphysiological administration, altering the plasma lipid profile. Taurine, a conditionally-essential amino acid often used in dietary supplements, was acknowledged to delay the onset and progression of atherogenesis, and to mitigate hyperlipidemia. The aim of the present study was to verify if taurine could prevent the alterations induced by concomitant chronic administration of high doses of AAS nandrolone decanoate (DECA) in rats. Materials and Methods: Thirty-two male Wistar rats, assigned to 4 equal groups, were treated for 12 weeks either with DECA (A group), taurine (T group), both DECA and taurine (AT group) or vehicle (C group). Plasma triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic triglycerides (TGh) and liver non-esterified fatty acids (NEFA) were then determined. Results: DECA elevated TG level in A group vs. control (p = 0.01), an increase prevented by taurine association in AT group (p = 0.04). DECA decreased HDL-C in A group vs. control (p = 0.02), while taurine tended to increase it in AT group. DECA decreased TGh (p = 0.02) in A group vs. control. Taurine decreased TGh in T (p = 0.004) and AT (p < 0.001) groups vs. control and tended to lower NEFA (p = 0.08) in AT group vs. A group. Neither DECA, nor taurine influenced TC and LDL-C levels. Conclusions: Taurine partially prevented the occurrence of DECA negative effects on lipid profile, suggesting a therapeutic potential in several conditions associated with chronic high levels of plasma androgens, such as endocrine disorders or AAS-abuse.

Ethanol exposed maturing rat cerebellar granule cells show impaired energy metabolism and increased cell death after oxygen-glucose deprivation.

Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells (CGCs) and on their response to oxygen-glucose deprivation (OGD). Primary CGC cultures were exposed to ethanol (100 mM in culture medium) or to control ethanol-free medium starting day one in vitro (DIV1). At DIV8, the expression of ATP synthase gene ATP5g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5g3 expression was reduced by 12-fold (P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values (P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values (P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.