Short-Term Alterations in Behavior and Astroglial Function After Intracerebroventricular Infusion of Methylglyoxal in Rats.

Methylglyoxal (MG) is a by-product of glycolysis. In pathological conditions, particularly diabetes mellitus, this molecule is unbalanced, causing widespread protein glycation. In addition to protein glycation, other effects resulting from high levels of MG in the central nervous system may involve the direct modulation of GABAergic and glutamatergic neurotransmission, with evidence suggesting that the effects of MG may be related to behavioral changes and glial dysfunction. In order to evaluate the direct influence of MG on behavioral and biochemical parameters, we used a high intracerebroventricular final concentration (3 µM/µL) to assess acute effects on memory and locomotor behavior in rats, as well as the underlying alterations in glutamatergic and astroglial parameters. MG induced, 12 h after injection, a decrease in locomotor activity in the Open field and anxiolytic effects in rats submitted to elevated plus-maze. Subsequently, 36 h after surgery, MG injection also induced cognitive impairment in both short and long-term memory, as evaluated by novel object recognition task, and in short-term spatial memory, as evaluated by the Y-maze test. In addition, hippocampal glutamate uptake decreased and glutamine synthetase activity and glutathione levels diminished during seventy-two hours after infusion of MG. Interestingly, the astrocytic protein, S100B, was increased in the cerebrospinal fluid, accompanied by decreased hippocampal S100B mRNA expression, without any change in protein content. Taken together, these results may improve our understanding of how this product of glucose metabolism can induce the brain dysfunction observed in diabetic patients, as well as in other neurodegenerative conditions, and further defines the role of astrocytes in disease and therapeutics.

Neuroprotective Effects of Guanosine Administration on In Vivo Cortical Focal Ischemia in Female and Male Wistar Rats.

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification. Immediately after surgeries, the ischemic animals were treated with GUO or a saline solution. Open field and elevated plus maze tasks were conducted with ischemic and naïve animals. Cylinder task, immunohistochemistry and infarct volume analyses were conducted only with ischemic animals. Female GUO groups achieved a full recovery of the forelimb symmetry at 28-35 days after the insult, while male GUO groups only partially recovered at 42 days, in the final evaluation. The ischemic insult affected long-term memory habituation to novelty only in female groups. Anxiety-like behavior, astrocyte morphology and infarct volume were not affected. Regardless the estrous cycle, the ischemic injury affected differently female and male animals. Thus, this study points that GUO is a potential neuroprotective compound in experimental stroke and that more studies, considering the estrous cycle, with both genders are recommended in future investigation concerning brain diseases.

A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease.

BACKGROUND: Because lithium exerts neuroprotective effects in preclinical models of polyglutamine disorders, our objective was to assess the safety and efficacy of lithium carbonate (0.5-0.8 milliequivalents per liter) in patients with Machado-Joseph disease (spinocerebellar ataxia type 3 [MJD/SCA3]). METHODS: For this phase 2, single-center, double-blind, parallel, placebo-controlled trial (ClinicalTrials.gov identifier NCT01096082), 62 patients who had MJD/SCA3 with a disease duration ≤10 years and an independent gait were randomly assigned (1:1) to receive either lithium or placebo. RESULTS: After 24 weeks, 169 adverse events were reported, including 50.3% in the lithium group (P = 1.00; primary safety outcome). Sixty patients (31 in the placebo group and 29 in the lithium group) were analyzed for efficacy (intention-to-treat analysis). Mean progression between groups did not differ according to scores on the Neurological Examination Score for the Assessment of Spinocerebellar Ataxia (NESSCA) after 48 weeks (-0.35; 95% confidence interval, -1.7 to 1.0; primary efficacy outcome). The lithium group exhibited minor progression on the PATA speech-rate (P = 0.002), the nondominant Click Test (P = 0.023), the Spinocerebellar Ataxia Functional Index (P = 0.003), and the Composite Cerebellar Functional Score (P = 0.029). CONCLUSIONS: Lithium was safe and well tolerated, but it had no effect on progression when measured using the NESSCA in patients with MJD/SCA3. This slowdown in secondary outcomes deserves further clarification.

Pristanic acid provokes lipid, protein, and DNA oxidative damage and reduces the antioxidant defenses in cerebellum of young rats.

Zellweger syndrome (ZS) and some peroxisomal diseases are severe inherited disorders mainly characterized by neurological symptoms and cerebellum abnormalities, whose pathogenesis is poorly understood. Biochemically, these diseases are mainly characterized by accumulation of pristanic acid (Prist) and other fatty acids in the brain and other tissues. In this work, we evaluated the in vitro influence of Prist on redox homeostasis by measuring lipid, protein, and DNA damage, as well as the antioxidant defenses and the activities of aconitase and α-ketoglutarate dehydrogenase in cerebellum of 30-day-old rats. The effect of Prist on DNA damage was also evaluated in blood of these animals. Some parameters were also evaluated in cerebellum from neonatal rats and in cerebellum neuronal cultures. Prist significantly increased malondialdehyde (MDA) levels and carbonyl formation and reduced sulfhydryl content and glutathione (GSH) concentrations in cerebellum of young rats. It also caused DNA strand damage in cerebellum and induced a high micronuclei frequency in blood. On the other hand, this fatty acid significantly reduced α-ketoglutarate dehydrogenase and aconitase activities in rat cerebellum. We also verified that Prist-induced increase of MDA levels was totally prevented by melatonin and attenuated by α-tocopherol but not by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester, indicating the involvement of reactive oxygen species in this effect. Cerebellum from neonate rats also showed marked alterations of redox homeostasis, including an increase of MDA levels and a decrease of sulfhydryl content and GSH concentrations elicited by Prist. Finally, Prist provoked an increase of dichlorofluorescein (DCFH) oxidation in cerebellum-cultivated neurons. Our present data indicate that Prist compromises redox homeostasis in rat cerebellum and blood and inhibits critical enzymes of the citric acid cycle that are susceptible to free radical attack. The present findings may contribute to clarify the pathogenesis of the cerebellar alterations observed in patients affected by ZS and some peroxisomal disorders in which Prist is accumulated.

Cellular senescence induced by prolonged subculture adversely affects glutamate uptake in C6 lineage.

Several researchers have recently used C6 cells to evaluate functional properties of high-affinity glutamate transporters. However, it has been demonstrated that this lineage suffers several morphological and biochemical alterations according to the number of passages in culture. Currently, there are no reports showing whether functional properties of high-affinity glutamate transporters comply with these sub culturing-dependent modifications. The present study aimed to compare the functional properties of high-affinity glutamate transporters expressed in early (EPC6) and late (LPC6) passage C6 cells through a detailed pharmacological and biochemical characterization. Between 60-180 min of L-[(3)H]glu incubation, LPC6 presented an intracellular [(3)H] 55% lower than EPC6. Both cultures showed a time-dependent increase of intracellular [(3)H] reaching maximal levels at 120 min. Cultures incubated with D-[(3)H]asp showed a time-dependent increase of [(3)H] until 180 min. Moreover, LPC6 have a D-[(3)H]asp-derived intracellular [(3)H] 30-45% lower than EPC6 until 120 min. Only EAAT3 was immunodetected in cultures and its total content was equal between them. PMA-stimulated EAAT3 trafficking to membrane increased 50% of L-[(3)H]glu-derived intracellular [(3)H] in EPC6 and had no effect in LPC6. LPC6 displayed characteristics that resemble senescence, such as high ß-Gal staining, cell enlargement and increase of large and regular nuclei. Our results demonstrated that LPC6 exhibited glutamate uptake impairment, which may have occurred due to its inability to mobilize EAAT3 to cell membrane. This profile might be related to senescent process observed in this culture. Our results suggest that LPC6 cells are an inappropriate glial cellular model to investigate the functional properties of high-affinity glutamate transporters.

Disruption of brain redox homeostasis in glutaryl-CoA dehydrogenase deficient mice treated with high dietary lysine supplementation.

Deficiency of glutaryl-CoA dehydrogenase (GCDH) activity or glutaric aciduria type I (GA I) is an inherited neurometabolic disorder biochemically characterized by predominant accumulation of glutaric acid and 3-hydroxyglutaric acid in the brain and other tissues. Affected patients usually present acute striatum necrosis during encephalopathic crises triggered by metabolic stress situations, as well as chronic leukodystrophy and delayed myelination. Considering that the mechanisms underlying the brain injury in this disease are not yet fully established, in the present study we investigated important parameters of oxidative stress in the brain (cerebral cortex, striatum and hippocampus), liver and heart of 30-day-old GCDH deficient knockout (Gcdh(-/-)) and wild type (WT) mice submitted to a normal lysine (Lys) (0.9% Lys), or high Lys diets (2.8% or 4.7% Lys) for 60 h. It was observed that the dietary supplementation of 2.8% and 4.7% Lys elicited noticeable oxidative stress, as verified by an increase of malondialdehyde concentrations (lipid oxidative damage) and 2-7-dihydrodichlorofluorescein (DCFH) oxidation (free radical production), as well as a decrease of reduced glutathione levels and alteration of various antioxidant enzyme activities (antioxidant defenses) in the cerebral cortex and the striatum, but not in the hippocampus, the liver and the heart of Gcdh(-/-) mice, as compared to WT mice receiving the same diets. Furthermore, alterations of oxidative stress parameters in the cerebral cortex and striatum were more accentuated in symptomatic, as compared to asymptomatic Gcdh(-/-) mice exposed to 4.7% Lys overload. Histopathological studies performed in the cerebral cortex and striatum of these animals exposed to high dietary Lys revealed increased expression of oxidative stress markers despite the absence of significant structural damage. The results indicate that a disruption of redox homeostasis in the cerebral cortex and striatum of young Gcdh(-/-) mice exposed to increased Lys diet may possibly represent an important pathomechanism of brain injury in GA I patients under metabolic stress.

Selenium compounds prevent amyloid ß-peptide neurotoxicity in rat primary hippocampal neurons.

Neuropathological hallmarks of Alzheimer's disease (AD) include amyloid plaque formation, neurofibrillary tangles, neuronal and synaptic loss. This study aims to identify the neuroprotective effects of the selenium compounds on the neurotoxicity of amyloid ß(1-42) in primary cultures of murine hippocampal neurons. Samples were subjected to immunocytochemistry and western blotting techniques to determine the role of treatments on neuronal viability and synaptic protein SNAP-25. We observed a reduced cell viability amyloid ß-peptide (1-42)-induced. When cells were co-treated with amyloid ß-peptide (1-42) and selenium compounds, we verified a strong increase in relative cell viability and in the level of synaptic marker synaptosomal-associated protein SNAP-25 induced by selenium compounds.

Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration.

In the present work we evaluated a variety of indicators of oxidative stress in distinct brain regions (striatum, cerebral cortex and hippocampus), the liver, and heart of 30-day-old glutaryl-CoA dehydrogenase deficient (Gcdh(-/-)) mice. The parameters evaluated included thiobarbituric acid-reactive substances (TBA-RS), 2-7-dihydrodichlorofluorescein (DCFH) oxidation, sulfhydryl content, and reduced glutathione (GSH) concentrations. We also measured the activities of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD). Under basal conditions glutaric (GA) and 3-OH-glutaric (3OHGA) acids were elevated in all tissues of the Gcdh(-/-) mice, but were essentially absent in WT animals. In contrast there were no differences between WT and Gcdh(-/-) mice in any of the indicators or oxidative stress under basal conditions. Following a single intra-peritoneal (IP) injection of lysine (Lys) there was a moderate increase of brain GA concentration in Gcdh(-/-) mice, but no change in WT. Lys injection had no effect on brain 3OHGA in either WT or Gcdh(-/-) mice. The levels of GA and 3OHGA were approximately 40% higher in striatum compared to cerebral cortex in Lys-treated mice. In the striatum, Lys administration provoked a marked increase of lipid peroxidation, DCFH oxidation, SOD and GR activities, as well as significant reductions of GSH levels and GPx activity, with no alteration of sulfhydryl content, CAT and G6PD activities. There was also evidence of increased lipid peroxidation and SOD activity in the cerebral cortex, along with a decrease of GSH levels, but to a lesser extent than in the striatum. In the hippocampus only mild increases of SOD activity and DCFH oxidation were observed. In contrast, Lys injection had no effect on any of the parameters of oxidative stress in the liver or heart of Gcdh(-/-) or WT animals. These results indicate that in Gcdh(-/-) mice cerebral tissue, particularly the striatum, is at greater risk for oxidative stress than peripheral tissues following Lys administration.

Reduction of Na+, K+-ATPase activity and expression in cerebral cortex of glutaryl-CoA dehydrogenase deficient mice: a possible mechanism for brain injury in glutaric aciduria type I.

Mitochondrial dysfunction has been proposed to play an important role in the neuropathology of glutaric acidemia type I (GA I). However, the relevance of bioenergetics disruption and the exact mechanisms responsible for the cortical leukodystrophy and the striatum degeneration presented by GA I patients are not yet fully understood. Therefore, in the present work we measured the respiratory chain complexes activities I-IV, mitochondrial respiratory parameters state 3, state 4, the respiratory control ratio and dinitrophenol (DNP)-stimulated respiration (uncoupled state), as well as the activities of α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and Na+, K+-ATPase in cerebral cortex, striatum and hippocampus from 30-day-old Gcdh-/- and wild type (WT) mice fed with a normal or a high Lys (4.7%) diet. When a baseline (0.9% Lys) diet was given, we verified mild alterations of the activities of some respiratory chain complexes in cerebral cortex and hippocampus, but not in striatum from Gcdh-/- mice as compared to WT animals. Furthermore, the mitochondrial respiratory parameters and the activities of α-KGDH and CK were not modified in all brain structures from Gcdh-/- mice. In contrast, we found a significant reduction of Na(+), K(+)-ATPase activity associated with a lower degree of its expression in cerebral cortex from Gcdh-/- mice. Furthermore, a high Lys (4.7%) diet did not accentuate the biochemical alterations observed in Gcdh-/- mice fed with a normal diet. Since Na(+), K(+)-ATPase activity is required for cell volume regulation and to maintain the membrane potential necessary for a normal neurotransmission, it is presumed that reduction of this enzyme activity may represent a potential underlying mechanism involved in the brain swelling and cortical abnormalities (cortical atrophy with leukodystrophy) observed in patients affected by GA I.

Marked reduction of Na(+), K(+)-ATPase and creatine kinase activities induced by acute lysine administration in glutaryl-CoA dehydrogenase deficient mice.

Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase activity leading to accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3HGA) acids in the brain and other tissues. Affected patients usually present with hypotonia and brain damage and acute encephalopathic episodes whose pathophysiology is not yet fully established. In this study we investigated important parameters of cellular bioenergetics in brain, heart and skeletal muscle from 15-day-old glutaryl-CoA dehydrogenase deficient mice (Gcdh(-/-)) submitted to a single intra-peritoneal injection of saline (Sal) or lysine (Lys - 8 µmol/g) as compared to wild type (WT) mice. We evaluated the activities of the respiratory chain complexes II, II-III and IV, α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and synaptic Na(+), K(+)-ATPase. No differences of all evaluated parameters were detected in the Gcdh(-/-) relatively to the WT mice injected at baseline (Sal). Furthermore, mild increases of the activities of some respiratory chain complexes (II-III and IV) were observed in heart and skeletal muscle of Gcdh(-/-) and WT mice after Lys administration. However, the most marked effects provoked by Lys administration were marked decreases of the activities of Na(+), K(+)-ATPase in brain and CK in brain and skeletal muscle of Gcdh(-/-) mice. In contrast, brain α-KGDH activity was not altered in WT and Gcdh(-/-) injected with Sal or Lys. Our results demonstrate that reduction of Na(+), K(+)-ATPase and CK activities may play an important role in the pathogenesis of the neurodegenerative changes in GA I.

High-glucose and S100B stimulate glutamate uptake in C6 glioma cells.

Diabetes mellitus is a disease associated with several changes in the central nervous system, including oxidative stress and abnormal glutamatergic neurotransmission, and the astrocytes play an essential role in these alterations. In vitro studies of astroglial function have been performed using cultures of primary astrocytes or C6 glioma cells. Herein, we investigated glutamate uptake, glutamine synthetase and S100B secretion in C6 glioma cells cultured in a high-glucose environment, as well as some parameters of oxidative stress and damage. C6 glioma cells, cultured in 12 mM glucose medium, exhibited signals of oxidative and nitrosative stress similar to those found in diabetes mellitus and other models of diabetic disease (decrease in glutathione, elevated NO, DNA damage). Interestingly, we found an increase in glutamate uptake and S100B secretion, and a decrease in glutamine synthetase, which might be linked to the altered glutamatergic communication in diabetes mellitus. Moreover, glutamate uptake in C6 glioma cells, like primary astrocytes, was stimulated by extracellular S100B. Aminoguanidine partially prevented the glial alterations induced by the 12 mM glucose medium. Together, these data emphasize the relevance of astroglia in diabetes mellitus, as well as the importance of glial parameters in the evaluation of diabetic disease progression and treatment.

Zika virus-induced brain malformations in chicken embryos.

BACKGROUND: Zika virus (ZIKV) was confirmed to be related to microcephaly in 2016. However, there is still a need for understanding the embryonic morphological changes induced by ZIKV and when they occur. Here, chicken embryos were chosen as experimental model of ZIKV to evaluate virus-associated morphological alterations that might take place during embryonic development. METHODS: A screening with different viral doses was conducted in embryos at HH Stage 10-12 (E1.5) as well as a follow up of the first 5 days postinfection (dpi) was performed to observe the main morphologic changes post ZIKV infection. RESULTS: ZIKV exposed embryos presented a higher prevalence of mortality and defects such as brain malformation when compared to controls. Moreover, we observed that the phenotypes become more evident at 4dpi, when the viral load quantification reaches a peak. CONCLUSIONS: We found that ZIKV exposed embryos presented a high prevalence of mortality and central nervous system (CNS) abnormalities in a dose-dependent manner. The phenotype was more evident 4 days postinfection, when the viral load quantification reached a peak.

The Brazilian-Portuguese version of the Sleep Hygiene Index (SHI): validity, reliability and association with depressive symptoms and sleep-related outcomes.

OBJECTIVE: To translate the Sleep Hygiene Index (SHI) to Brazilian Portuguese, to describe its psychometric properties and to show its association with sleep quality, daytime sleepiness, risk for sleep apnea and depressive symptoms. METHODS: Thirty subjects participated in the cultural adaptation and the item clarity evaluation. Twenty subjects answered the instrument in three different time-points for test-retest reliability. Eighty adult workers completed the SHI, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Beck Depression Inventory (BDI) and the STOP-BANG (S-B). RESULTS: SHI shows an acceptable internal consistency (Cronbach's α=0.75), as well as a high reproducibility (intraclass correlation=0.972, p<0.01). The three final factors of confirmatory factor analysis extract an average of 48.22% of the total sample variance. Worse sleep hygiene (higher SHI score) correlated with poor sleep quality (r=0.398, p<0.001), excessive daytime sleepiness (r=0.406, p<0.001) and depressive symptoms (r=0.324, p=0.003). No correlations with S-B were found. CONCLUSIONS: SHI presents satisfactory-to-optimal psychometric properties. This instrument is useful for treatment planning and management of sleep hygiene practices. Thus, it represents a reliable way of assessing sleep hygiene quantitatively in both research and clinical settings.

Guanosine protects against Ca2+-induced mitochondrial dysfunction in rats.

Mitochondria play an important role in cell life and in the regulation of cell death. In addition, mitochondrial dysfunction contributes to a wide range of neuropathologies. The nucleoside Guanosine (GUO) is an endogenous molecule, presenting antioxidant properties, possibly due to its direct scavenging ability and/or from its capacity to activate the antioxidant defense system. GUO demonstrate a neuroprotective effect due to the modulation of the glutamatergic system and maintenance of the redox system. Thus, considering the few studies focused on the direct effects of GUO on mitochondrial bioenergetics, we designed a study to evaluate the in vitro effects of GUO on rat mitochondrial function, as well as against Ca2+-induced impairment. Our results indicate that GUO prevented mitochondrial dysfunction induced by Ca2+ misbalance, once GUO was able to reduce mitochondrial swelling in the presence of Ca2+, as well as ROS production and hydrogen peroxide levels, and to increase manganese superoxide dismutase activity, oxidative phosphorylation and tricarboxylic acid cycle activities. Our study indicates for the first time that GUO could direct prevent the mitochondrial damage induced by Ca2+ and that these effects were not related to its scavenging properties. Our data indicates that GUO could be included as a new pharmacological strategy for diseases linked to mitochondrial dysfunction.

Neuroinflammation and Neuromodulation in Neurological Diseases.

Neuroimmunology is a relatively young science. This discipline has emerged today from the research field as a mature and fully developed innovative research area that integrates not only pure topics of neuroimmunology, but also expands on wider fields such as neuroplasticity, neuronal reserve and neuromodulation in association with clinical events, amongst which behavioral disorders stand out. The Cuban School of Neuroimmunology-a recent meeting that took place in Havana, Cuba-focused on topics based on the molecular mechanisms of neuroinflammation in neurological disorders involving behavioral manifestations, such as multiple sclerosis (MS), autism, cerebellar ataxias, Alzheimer´s disease and stroke among others, as well as on the use of new interventional technologies in neurology. Professor Luis Velazquez, from the Cuban Academy of Sciences, dictated an interesting lecture on Spinocerebellar ataxias, a genetic disorder where recent hypotheses related to the influence of neuroinflammation as a neurobiological factor influencing the progression of this disease have emerged. At the same time, the use of new interventional technologies in neurology was discussed, including those referring to novel disease modifying therapies in the course of MS and the use of transcranial magnetic stimulation in several neurological diseases, the latter reinforcing how interventional strategies in the form of non-invasive bran stimulation can contribute to physical rehabilitation in neurology. This paper summarizes the highlights of the most relevant topics presented during the First Cuban School of Neuroimmunology, organized by the Cuban Network of Neuroimmunology, held in June 2019.

O poder sobre a vida: os corpos regidos pela prática biomédica versus corpos de intensidades / The power over life: bodies governed by biomedical practice versus intensity bodies

Neste artigo, discuto a questão da materialidade organicista do corpo contra um corpo de intensidades. De acordo com Separavich e Canesqui (2010), os estudos de Marcel Mauss (2003 [1934]) e Margaret Mead (2000 [1935]) "revelou que, embora se possa atribuir uma materialidade universal ao corpo, definições, disposições corporais e seus significados são múltiplos. Como resultado dessa heterogeneidade nas formas de conceber corpo, as concepções do que seja saúde e doença também múltiplas tradições" (p. 251). De acordo com Cecil G. Helman (1994) para "os membros de todas as sociedades, o corpo humano é mais do que um simples organismo físico oscilando entre a saúde e a doença. É também o foco de um conjunto de crenças sobre seu significado social e psicológico, estrutura e funcionamento. A expressão 'imagem corporal' é usada para descrever todas as maneiras pelas quais um indivíduo conceitua e experimenta seu próprio corpo, consciente ou inconscientemente" (p. 30), variando com cada sociedade e momento histórico em que se definem: incluem crenças sobre a forma e o tamanho ideal do corpo, crenças sobre sua estrutura e crenças sobre suas funções. Pretendo refletir sobre o corpo, trazendo alguns elementos históricos para chamar a atenção para a ocorrência de certas condições ­ conhecimento médico e outros aspectos sócio-históricos ­ entrelaçada com a produção de práticas e intervenções médicas, no corpo, assim como no governo da vida, com a intenção de chamar a atenção para as práticas médicas integrativas que são a partir de uma visão do corpo de intensidades.

In this article, I discuss the issue of the organicist materiality of the body versus a body of intensities. According to Separavich and Canesqui (2010), the studies of Marcel Mauss (2003 [1934]) and Margaret Mead (2000 [1935]) "revealed that, although a universal materiality can be attributed to the body, definitions, bodily dispositions and their meanings are manifold. As a result of this heterogeneity in the ways of conceiving the body, the conceptions of what health and disease are also have multiple traditions" (p. 251). According to Cecil G. Helman (1994) for "the members of all societies, the human body is more than a simple physical organism oscillating between health and disease. It is also the focus of a set of beliefs about its social and psychological meaning, structure and functioning. The expression 'body image' is used to describe all the ways in which an individual conceptualizes and experiences his own body, consciously or unconsciously" (p. 30), varying with each society and historical moment in which they are defined: they include beliefs about ideal body shape and size, beliefs about its internal structure, and beliefs about its functions. I intend to reflect on the body, bringing some historical elements to draw attention to the occurrence of certain conditions - medical knowledge and other socio-historical aspects - intertwined with the production of medical practices and interventions, in the body, as well as in the government of life, with the intention of drawing attention to integrative medical practices that are based on a vision of the body of intensities.

Long-term effect of uncomplicated Plasmodium berghei ANKA malaria on memory and anxiety-like behaviour in C57BL/6 mice.

BACKGROUND: Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria. METHODS: Plasmodium berghei ANKA-infected and non-infected C57BL/6 mice were used. Development of cerebral malaria was prevented by chloroquine treatment starting on the fourth day of infection. The control group (non-infected mice) were treated with PBS. The effect of uncomplicated malaria infection on locomotor habituation, short and long-term memory and anxious-like behaviour was evaluated 64 days after parasite clearance in assays including open field, object recognition, Y-maze and light/dark tasks. RESULTS: Plasmodium berghei ANKA-infected mice showed significant long-lasting disturbances reflected by a long-term memory-related behaviour on open field and object recognition tasks, accompanied by an anxious-like phenotype availed on open field and light-dark tasks. CONCLUSIONS: Long-term neurocognitive sequels may follow an uncomplicated malaria episode in an experimental model prone to develop cerebral malaria, even if the infection is treated before the appearance of clinical signs of cerebral impairment.

Brain injury markers (S100B and NSE) in chronic cocaine dependents.

OBJECTIVE: Studies have shown signs of brain damage caused by different mechanisms in cocaine users. The serum neuron specific enolase and S100B protein are considered specific biochemical markers of neuronal and glial cell injury. This study aimed at comparing blood levels of S100B and NSE in chronic cocaine users and in volunteers who did not use cocaine or other illicit drugs. METHOD: Twenty subjects dependent on cocaine but not on alcohol or marijuana, and 20 non-substance using controls were recruited. Subjects were selected by consecutive and non-probabilistic sampling. Neuron specific enolase and S100B levels were determined by luminescence assay. RESULTS: Cocaine users had significantly higher scores than controls in all psychiatric dimensions of the SCL-90 and had cognitive deficits in the subtest cubes of WAIS and the word span. Mean serum S100B level was 0.09 +/- 0.04 microg/l among cocaine users and 0.08 +/- 0.04 microg/l among controls. Mean serum neuron specific enolase level was 9.7 +/- 3.5 ng/l among cocaine users and 8.3 +/- 2.6 ng/l among controls. CONCLUSIONS: In this first study using these specific brain damage markers in cocaine users, serum levels of S100B and neuron specific enolase were not statistically different between cocaine dependent subjects and controls.

Teste de Progresso: ausência de alunos de Medicina é sugestiva de mau desempenho acadêmico / Progress Test: medical student absenteeism is suggestive of poor academic performance

Resumo: Introdução: Não se sabe se a ausência de estudantes de Medicina ao Teste de Progresso (TP) se dá de forma aleatória ou por alguma característica sistemática deles, o que poderia influenciar a representatividade dos resultados obtidos pelos participantes. Objetivo: Este estudo teve como objetivos comparar os índices de desempenho acadêmico, no curso de Medicina da UFSC, dos alunos presentes e ausentes ao TP em 2019; propor uma maneira de estimar, a partir desses índices, quais seriam as notas dos faltantes se tivessem participado do TP; e identificar fatores associados à ausência ao TP. Método: Foram comparadas as médias dos índices de desempenho acadêmico, globais e nas diferentes fases (semestres) dos grupos de alunos presentes e ausentes ao TP, utilizando teste t de Student para amostras independentes. Por meio de uma técnica de regressão linear, foram imputadas as prováveis notas no TP ao grupo de alunos ausentes. Resultado: As médias globais dos três indicadores acadêmicos foram significativamente menores nos alunos ausentes ao TP (p variando de < 0,03 a < 0,0001); em dez das 11 fases (semestres) analisadas do curso, os indicadores acadêmicos dos faltosos foram piores do que dos presentes. A imputação de notas no TP aos ausentes permitiu verificar que existe correlação (R = 0,62) entre a porcentagem destes e a diferença de notas entre os grupos que realizaram e os que faltaram ao TP. Entre os alunos do gênero masculino, 25,8% não fizeram o TP, enquanto no gênero feminino foram 16,6% (diferença com p < 0,01). Conclusão: A ausência de alunos ao TP não se dá de forma aleatória. Entre os faltosos, há uma tendência sistemática de existirem alunos com piores índices de desempenho acadêmico. O uso de imputação múltipla de dados evidencia uma correlação entre a porcentagem de faltosos e a diferença na média da nota no TP, desse grupo, comparada à média da nota dos participantes. A proporção de homens que faltaram ao TP foi significativamente maior do que a de mulheres.

Abstract: Introduction: It is not known whether the absence of medical students at the Progress Test (PT) is random event or if it due to some systematic characteristic of the students, which could influence the representativeness of the results obtained by the participants. Objectives: 1) to compare the academic performance indexes, in UFSC Medical School, of students who were present and absent from the PT in 2019; 2) to propose a way to estimate, based on these indexes, what the absentee's grades would be if they had participated in the PT; 3) to identify factors associated with absence from the PT. Method: The averages of academic performance indexes, overall and in the different phases (semesters) in the groups of students who were present and absent from the PT, were compared using Student's t test for independent samples. Using a linear regression technique, the probable PT scores were assigned to the group of absent students. Results: The global averages of the three academic indicators were significantly lower in students absent from the PT (p ranging from < 0.03 to < 0.0001); in 10 of the 11 analyzed course phases (semesters), the academic indicators of absentees were worse than those present at the test. The attribution of PT grades to the absentees allowed us to verify that there is a correlation (R=0.62) between the percentage of these students and the difference in grades between the groups that took and those that did not take the PT. Among male students, 25.8% did not attend the PT, while among female students the number of absentees was 16.6% (difference with p <0.01). Conclusions: The absence of students at the PT does not occur randomly. Among the absentees, there is a systematic tendency to have students with worse academic performance. The use of multiple imputation of data demonstrate a correlation between the percentage of absentees and the difference in the average of grades in the PT of this group, compared to the average of the participants' grades. The proportion of male students who missed the PT was significantly higher than that of female students.

α-Ketoadipic Acid and α-Aminoadipic Acid Cause Disturbance of Glutamatergic Neurotransmission and Induction of Oxidative Stress In Vitro in Brain of Adolescent Rats.

Tissue accumulation of α-ketoadipic (KAA) and α-aminoadipic (AAA) acids is the biochemical hallmark of α-ketoadipic aciduria. This inborn error of metabolism is currently considered a biochemical phenotype with uncertain clinical significance. Considering that KAA and AAA are structurally similar to α-ketoglutarate and glutamate, respectively, we investigated the in vitro effects of these compounds on glutamatergic neurotransmission in the brain of adolescent rats. Bioenergetics and redox homeostasis were also investigated because they represent fundamental systems for brain development and functioning. We first observed that AAA significantly decreased glutamate uptake, whereas glutamate dehydrogenase activity was markedly inhibited by KAA in a competitive fashion. In addition, AAA and more markedly KAA induced generation of reactive oxygen and nitrogen species (increase of 2',7'-dichloroflurescein (DCFH) oxidation and nitrite/nitrate levels), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione (GSH)) and aconitase activity. Furthermore, KAA-induced lipid peroxidation and GSH decrease were prevented by the antioxidants α-tocopherol, melatonin, and resveratrol, suggesting the involvement of reactive species in these effects. Noteworthy, the classical inhibitor of NMDA glutamate receptors MK-801 was not able to prevent KAA-induced and AAA-induced oxidative stress, determined by DCFH oxidation and GSH levels, making unlikely a secondary induction of oxidative stress through overstimulation of glutamate receptors. In contrast, KAA and AAA did not significantly change brain bioenergetic parameters. We speculate that disturbance of glutamatergic neurotransmission and redox homeostasis by KAA and AAA may play a role in those cases of α-ketoadipic aciduria that display neurological symptoms.