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2020
 Thèses 1 GEOVAN MENEZES DE SOUSA JÚNIOR Mediation and moderation analyses of mindfulness trait and training on affect, anxiety and stress measures in healthy young adults Leader : MARIA BERNARDETE CORDEIRO DE SOUSA MEMBRES DE LA BANQUE : DRAULIO BARROS DE ARAUJO LUIZ CARLOS SERRAMO LOPEZ MARIA BERNARDETE CORDEIRO DE SOUSA Data: 16 janv. 2020 Afficher le Résumé Contemporary lifestyle has a strong impact on people's health and mental well-being, as suggested by current World Health Organization indicators. Such impairment is generally linked to the deregulation of the psychophysiological mechanisms of stress response, given the variety and the frequency of stressful events to which the population is exposed daily. In this context, non-pharmacological interventions to reduce the impact of these agents have been used, including those that integrate the mind and body dimensions, such as mindfulness. This meditative practice, which has been implicated in reducing symptoms of anxiety, depression, and stress, is usually defined in terms of the ability to pay attention to the present moment with openness, acceptance, and kindness, being evaluated as a state or a trait. Thus, the present study aimed to demonstrate, through an exploratory approach, whether a brief practice of mindfulness depends on the trait or state of mindfulness, or both, and interferes with variables that express psychological well-being. Our hypotheses predict that (1) the high level of mindfulness is associated with better psychological well-being; (2) a brief practice of mindfulness reduces the indicators and increases the positive indicators of psychological well-being, and (3) these changes are mediated by practice-induced increase in state mindfulness. A sample consisted of healthy young university students (n = 40; 20 men) and measures associated with anxiety (STAI), affect (PANAS), stress (PSS, plasma cortisol), and mindfulness (state, SMS and trait, FFMQ) were collected. Initially, by means of a cluster analysis (k-means), these individuals were classified as high / low mindfulness trait, in which those with high trait presented lower levels of anxiety state and perceived stress. Additionally, the sample was tested by dividing it into a painting active control group (CG, n = 20) and a mindfulness training group (MG, n = 20) using a mixed variance analysis (between: group, within: session [before / after intervention]) to investigate the effect of the intervention between and within groups. Within GM there was a reduction in the anxiety state  and perceived stress in addition to an increase in state mindfulness after the practice. Within both groups there was a reduction in negative affect and plasma cortisol levels and no difference was found for positive affect. Between the two groups, despite the tendency of the GM to present lower levels of stress perceived after the intervention in relation to the CG, no difference was significant. Moderate mediation analysis showed that the increase in state mindfulness mediated an increase in positive affect and a decrease in perceived stress and cortisol  The mediating effect of state mindfulness in decreasing anxiety state occurs only in individuals with high mindfulness trait. Despite the limitations of the sample size and the exploratory nature of the study, which uses multiple tests for the same dataset, these results suggest that the mindfulness trait is associated with lower stress levels, and that a brief mindfulness-based intervention promotes attenuation of the negative psychophysiological response, and mediate increase in positive affect. These results point to a positive effect of a brief mindfulness practice in a specific group of individuals, and open perspectives for further investigation and its application in different populations. 2 ELIS BRISA DOS SANTOS Visualization of calcium dynamics in mouse neural circuits with epifluorescence mini microscopes and chronically  implanted lenses Leader : RICHARDSON NAVES LEAO MEMBRES DE LA BANQUE : DIEGO ANDRES LAPLAGNE EDUARDO BOUTH SEQUERRA FLAVIO FREITAS BARBOSA RICHARDSON NAVES LEAO Data: 3 févr. 2020 Afficher le Résumé Neurons are electrically and chemically excitable, when excited enough, several ions quickly move across the membrane, causing a depolarization. Among these ions, Ca2+ is the only one that in addition to participating in action potential is also biologically active, participating in various cellular events, acting primarily as a cellular messenger. Studying the role of Ca2+ in the various events was possible through the development of techniques that allowed to measure its dynamics, such as the development of optical tools, being the first generation composed of dyes and later, with the advent of molecular engineering, the genetically encoded calcium indicators (GECIs), composed by hybridization of a fluorescent protein linked to a sensor protein. From early dyes to the most current GECIs, many advances have been made in increasing temporal and spatial resolution, Ca2+ sensitivity, photobleaching resistance, decreased phototoxicity, and high signal-to-noise ratio. However, in vivo mammalian preparations remained a challenge. Currently, GCaMP variants are one of the most commonly used GECIs, which are composed of calmodulin as a sensor protein, linked to a green fluorescent protein (GFP). In this work we will evaluate GCaMP expression with different viral promoters and calcium signals in vivo, in records made with adult mice walking in a treadmill at different speeds, using chronically implanted lenses and epifluorescence cameras. 3 JOSÉ MEDEIROS DO NASCIMENTO FILHO Peripartum depression: Screening in women with a history of high maternal risk - analysis of hormonal, clinical and epidemiological factors.   Leader : MARIA BERNARDETE CORDEIRO DE SOUSA MEMBRES DE LA BANQUE : EMERSON ARCOVERDE NUNES MARIA BERNARDETE CORDEIRO DE SOUSA MARIA DA PENHA DE LIMA COUTINHO Data: 13 juil. 2020 Afficher le Résumé Major depressive disorder (MDD) is currently a public health problem, affecting more than 300 million people worldwide. This disorder is extremely important in the puerperal period, when women may develop depressive symptoms linked to variations in sexual hormones and in the hypothalamic-pituitary-adrenal axis, both changes associated with gestational status and peri-partum, with negative consequences for the mother, the newborn, or both. Several studies have shown that steroid and peptides hormones have modulatory effects on neural circuits associated with parental care, a behavior that is also influenced by genetic, socio-environmental and economic factors. Thus, the occurrence of depression in the postpartum period should be investigated more broadly in order to address these aspects. The objectives of this study were (1) to describe the characteristics of a sample of primiparous pregnant women in terms of socioeconomic aspects and prenatal epidemiology, and (2) to model the risk of depression in this sample. The experimental design consisted of a cross-sectional and quantitative study in which 116 women over 18 years old, with live birth fetuses, were interviewed within 48 hours after delivery. Socio-epidemiological questionnaire that also included prenatal quality questions, and two screening scales for depression - Pacient Health Questionnaire 9 (PHQ9, cut-off point 10) and Edinburgh Puerperal Depression Scale (EPDS, cut-off point 10) were used. The day after the questionnaires were applied, blood was collected to measure morning cortisol. The statistical analysis showed that the average age of the participants was 24.37 years (61.26%; n = 71) and that most of them had a family income of up to 1 minimum wage (75%; n = 84), and stable union (72.41%; n = 84), declaring that they receive too much or too much support from their partner. The general average of the number of prenatal consultations was 8.65 + 3,19) with consultations beginning at around 9.34 + 4,42 weeks ). Eighty women (68.96%)  stated that they had not been asked about their mood during the prenatal period. Only 13.80% (n = 16) women reported previous psychiatric problems. Of this total, 23.28% (n = 27) were positive on the EPDS and 52.59% (n = 61) were positive on the PHQ9. It was possible to collect samples for analysis of cortisol from 107 women. Of the total number of parturient women, 46 women with an income of up to 1 minimum wage were selected and divided into two groups: 21 participants who had a positive screening in EPDS and another 25 participants with both negative screenings (EPDS and PHQ9). Considering those 46 participants from both groups, the modeling of the risk of depression in the peripartum was performed using a logistic regression model (Model I). The risk factors found were younger age, lower levels of cortisol, presence of a previous psychiatric history, and support from the father. Another model, using the 107 participants (Model II), sought to identify the positive screening prediction. In this analysis, the positive predictive factors were family income of up to one minimum wage, residing in the state capital and previous psychiatric history. Based on the results obtained, adjustments to the high-risk prenatal program of the studied maternity will be proposed, and suggested recommendations for screening for depression in the immediate postpartum period, using the PHQ2 questionnaire, in order to allow an intervention in patients potentially depressed. 4 NATÁLIA CASTELO BRANCO MATOS Quantitative analysis of retinogeniculate gamma oscillations in the cat Leader : SERGIO TULIO NEUENSCHWANDER MACIEL MEMBRES DE LA BANQUE : JEROME PAUL ARMAND LAURENT BARON KERSTIN ERIKA SCHMIDT SERGIO TULIO NEUENSCHWANDER MACIEL Data: 26 nov. 2020 Afficher le Résumé Retinal gamma oscillations have been observed in a variety of vertebrates. Recent and former evidence points to their involvement in encoding stimulus properties such as size and continuity. To investigate these claims, we started by revisiting already established relationships between oscillation characteristics and different visual stimuli in the anesthetized animal. We analyzed single and multi-unit activity recorded from the retina and LGN of cats while they observed complex (short videos) and simple (light circles) stimuli. In follow-up experiments, the LGN of awake cats was also recorded. The animals were subsequently anesthetized with ketamine and later on, halothane. We observed that under natural stimuli and halothane anesthesia, the oscillatory response elicited by video stimuli was unreliable. It occurred in brief periods, which seemed to mainly reflect image contrast. Large circles presented to anesthetized cats, on the other hand, robustly generated gamma-band oscillations, with its strength modulated by luminance and stimulus size. Interestingly, in the awake or ketamine only anesthetized animals, no oscillations could be detected, although entrainment to the monitor refresh rate was observed up to 120 Hz. Furthermore, gamma oscillation in the cat's retina was dependent on halothane concentration. Gamma activity was drastically reduced as levels of halothane were decreased. Taken together, our results do not support a cognitive role for gamma oscillations in the retinogeniculate system. Thèses 1 GLEIDSON MENDES REBOUÇAS Differential diagnosis based on autonomic variables and speech structure among neuropsychiatric disorders using machine learning Leader : MARIA BERNARDETE CORDEIRO DE SOUSA MEMBRES DE LA BANQUE : EMERSON ARCOVERDE NUNES JOSÉ RODOLFO LOPES DE PAIVA CAVALCANTI MARIA BERNARDETE CORDEIRO DE SOUSA MARIO ANDRE LEOCADIO MIGUEL Melyssa Kellyane Cavalcanti Galdino SIDARTA TOLLENDAL GOMES RIBEIRO Data: 23 janv. 2020 Afficher le Résumé The study of the adaptive nature stress response shows the major participation of physiological mechanisms associated with the hypothalamic-pituitary-adrenal endocrine axis (HPA) and the Autonomic Nervous System (ANS), in its sympathetic and parasympathetic divisions, as well as the immune system. Individuals with differentneuropsychiatric disorders present signs and symptoms that suggest dysregulation of the ANS (dysautonomia) and the expression or form of oral speech. These occurrences are present in other disorders that are part of the psychophysiological spectrum that includes PTSD, AT and OCD. In this context, the objective of this study was to develop a diagnostic classification mathematical model for PTSD, based on the analysis of autonomic variables and discourse structure. We investigated 298 males aged 22 to 48 years allocated into four groups: PTSD (n = 76), AT (n = 77), OCD (n = 73) and Control (n = 72). The PCL-5, BAI and YBOCS questionnaires were used to obtain the psychometric data related respectively to PTSD, TA and OCD. The SpeechGraphs® software was used to analyze the representation of the word trajectory and to quantitatively characterize the speech complexification. An ECG signal (ADInstruments model PowerLab®) was used to analyze heart rate variability (HRV) and skin conductance (RGP). Machine learning techniques (Decision Tree and Naive Bayes) were employed to obtain the mathematical model. The model generated for PTSD classification based on HRV measurements presented accuracy of 92.3% (p <0.0001) and Kappa index of 89.7% with the generation of a decision algorithm using parasympathetic axis measurements (SDNN and RMSSD) and sympathetic (LF). The model generated for PTSD classification based on autonomic skin conductance (μS) measurements presented 96.6% accuracy (p <0.0001) and 95.4% Kappa index with the generation of a decision algorithm using measurements checked on the second one and 180 of the five-minute. The model generated for PTSD classification based on speech trajectory measurements presented accuracy of 80.9% (p <0.0001) and Kappa index of 71.4% with the generation of a decision algorithm using lexical diversity measures (Nodes), recurrence (RE, PE) and connectivity (LSC, LCC and L3). The classification in levels of severity of the disorder allowed the identification, by the k-means method, of 3 classes (degrees) of elevation for each variable. Models generated with autonomic measurements have better accuracy for PTSD classification and present the potential to be used as a more efficient method for diagnosis, future investigations into risk stratification, severity categorization and follow-up of the clinical evolution of this disorder. 2 THAWANN MALFATTI BORGES The role of activity of the dorsal cochlear nucleus in tinnitus perception in mice Leader : EMELIE KATARINA SVAHN LEAO MEMBRES DE LA BANQUE : EMELIE KATARINA SVAHN LEAO MARINE RAQUEL DINIZ DA ROSA NIVALDO ANTONIO PORTELA DE VASCONCELOS RICHARDSON NAVES LEAO RODRIGO NEVES ROMCY PEREIRA SERGIO TULIO NEUENSCHWANDER MACIEL Data: 27 mars 2020 Afficher le Résumé Noise-induced tinnitus is a phantom sound, perceived without a physical source, caused by over-exposure to loud noise. The dorsal cochlear nucleus (DCN), a region known to integrate somatosensory and auditory pathways, has been identified as a potential key structure in the generation of phantom sound perception. Here, we first target the output layer of the DCN using viral vectors containing the CaMKIIa (CaMKIIa) promoter to express optogenetic proteins and investigate how exciting (Channelrhodopsin-2, ChR2) or inhibiting (enhanced Archaerhodopsin 3.0, eArch3.0) those DCN cells affects the DCN circuitry response to sound. We found that optogenetic stimulation of DCN cells expressing CaMKIIa-ChR2 or CaMKIIa-Arch can distort DCN units responses to sound. Next, we chemogenetically decrease activity of the same subgroup of DCN neurons using the Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs) to investigate their role in tinnitus perception. Mice were exposed to loud noise (90dBSPL, 1h, followed by 2h of silence) to induce tinnitus. Auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) test were recorded two days before and two weeks after noise exposure to confirm tinnitus perception (significant decrease in GPIAS response) without permanent hearing loss. Activity of CaMKIIa-hM4Di+ neurons in the DCN was decreased by expressing and pharmacologically activating the hM4Di DREADDs. Perception of tinnitus was evaluated when inhibitory hM4Di DREADDs were activated by systemic clozapine-n-oxide (CNO, 0.5mg/kg) administration. We found CNO to decrease tinnitus-like responses (p = 0.038, n = 11 mice), compared to the control group that showed no improvement in GPIAS responses (control virus; CaMKIIa-YFP + CNO, p = 0.696, n = 7 mice). Unit recordings confirmed CNO to decrease DCN firing frequency, alter best frequency and broadness of response to sound. Next CaMKIIa-hM4Di-mCherry positive DCN neurons were instead chemogenetically inhibited during the noise exposure (n = 6 experimental and 6 control mice), but this did not prevent tinnitus induction, nor did CNO administration 2 weeks later improve gap-detection indicating tinnitus perception was not decreased. Our results suggest that CaMKIIa-hM4Di-mCherry positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice. 3 ANNIE DA COSTA SOUZA PSYCHEDELIC STATES AND SLEEP IN THE RAT BRAIN: BEHAVIORAL, ELECTROPHYSIOLOGICAL AND MOLECULAR STUDIES Leader : SIDARTA TOLLENDAL GOMES RIBEIRO MEMBRES DE LA BANQUE : SIDARTA TOLLENDAL GOMES RIBEIRO ADRIANO BRETANHA LOPES TORT RICHARDSON NAVES LEAO VITOR LOPES DOS SANTOS CLEITON LOPES AGUIAR VINICIUS ROSA COTA Data: 29 avr. 2020 Afficher le Résumé Classic psychedelics (or hallucinogens) are substances known for altering consciousness. Early experiments on several classic psychedelics demonstrated that their psychoactive effect is dependent on 5-HT2A and 5-HT1A serotonergic receptors, but due to the long prohibition of these drugs, little is known about their electrophysiological effects on the brain. In the current work I set out to investigate the effects of 5-MeO-DMT and d-LSD, two potent serotonergic agonists, on the local field potentials (LFP) recorded from the hippocampus and prefrontal cortex of rats. Typical behavioral alterations ~15 min after drug injection were observed, such as increased locomotion, increased space occupancy, and the occurrence of stereotyped behaviors (wet-dog shake, uncoordinated gaiting etc). Similar to previous results, LFP alterations were detected in prefrontal cortical areas (PFC), as well as in the hippocampus (HP). The power in the Theta (5-12 Hz) and Gamma band (30-100 Hz) decreased in the two areas within the first 30 min after (i.p. and i.c.v.) 5-MeO-DMT injection for all experiments, except for the highest dose of 5-MeO-DMT (i.c.v.) in the PFC. Likewise, we found a similar result for d-LSD in the long-term analysis, there was a decrease in the Gamma power after ~4h30min after d-LSD (i.p.) injection. We found that power in the delta (0.5-4 Hz) band did not change significantly. Moreover, coherence analysis revealed that 5-MeO-DMT (i.p.) increased the coherence between HP and PFC in the Delta and Theta range. Next, I assessed how similar the changes caused by classic psychedelics are to the changes observed across the sleep-wake cycle. State map analysis revealed that both substances promoted a shift in the spectral profile typical of waking (WK) towards that of slow-wave sleep (SWS) or intermediated sleep (IS)/REM. Although animals remain awake after being treated with psychedelics, it is not a normal WK in terms of the LFP spectral profile. While some of the results obtained corroborate previous studies (e.g., the decrease in gamma power in the PFC), I also found divergent results, such as the decrease in PFC theta power. Altogether, the results are novel and promote a better understanding of the neurophysiological alterations caused by classic hallucinogens. The second chapter of this thesis is dedicated to the investigation of the cognitive role of the distinct sleep stages in terms of the molecular (and electrophysiological) correlates. We hypothesized that the SWS and REM sleep play distinct roles in memory processing during sleep and that the phosphoproteomic profiles are as well distinct. More specifically, we screened the phosphorylated proteins of the somatosensory cortex and the hippocampus of during both sleep stages of animals that were exposed or not exposed to novelty in the previous waking. It is known that besides its restorative role, sleep plays an important role in memory consolidation and cognition. However little is known on the molecular mechanism that underlies this function, and which dynamic it would have across the different sleep stages (SWS and REM sleep). In a previous work of our group, we have demonstrated that phosphorylated CaMKIIalpha, a kinase protein related to synaptic plasticity, is down-regulated during SWS and up-regulated during REM sleep in the hippocampus of rats exposed to novelty in the previous waking. This work has motivated follow-up research with the question: which are the other proteins that modulated in a sleep stage-dependent manner? In order to answer this question, we made similar experiments using a proteomic approach looking for protein phosphorylation markers. We identified a total of 2334 proteins in both brain regions of HP and primary somatosensory cortex (S1). Among the identified proteins we found a variety that was significantly modulated across the sleep cycle.  The ontogenetic analysis revealed that the modulated proteins belong to several classes, for instance, cytoskeleton organization, RNA processing, calcium signalling pathways etc. In terms of quantitative analysis, the animals from slow-wave sleep group that were previously exposed to novelty presented 9 modulated proteins in the hippocampus, while 23 in the S1 region compared to non-exposed animals. In the same way, REM sleep exposed animals had 3 modulated proteins in the HP and 3 in the S1 compared to the non-exposed animals. Overall the results point that novelty-induced changes in protein phosphorylation levels are more pronounced in the S1 cortex than in HP, and that this seems to occur mainly during SWS. Possibly, this upward, as well as the downward modulation, could be related to the characteristics of the up and down state of the slow oscillations of SWS. On the other hand, during REM sleep, there are fewer modulated proteins. A variety of functions were identified and a great part of that refers to the general functioning of the neurons, especially during SWS. However, once that novelty is present, such stimuli would narrow the phosphorylation to a more specific/selective towards pathways related to sensory processing, mainly during REM sleep. Such an idea is corroborated by recent findings concerning the cognitive role of sleep. During REM sleep right after a motor learning, mice presented a synaptic pruning in the synapses that were ‘weakened’ during the task, while a little number of synapses were ‘strengthened
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