ICe - Artigos publicados em periódicos

URI Permanente para esta coleçãohttps://repositorio.ufrn.br/handle/1/6192

Repositório da produção científica do Instituto do Cérebro - ICe, da UFRN, Unidade Acadêmica Especializada em neurociências.

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Theta-encoded information flow from dorsal CA1 to prelimbic cortex drives memory reconsolidation
(Elsevier BV, 2025) Radiske, Andressa; Gonzalez, María Carolina; Rossato, Janine Inez; Ocazionez, Sergio Andrés Conde; Cammarota, Martín Pablo
Reconsolidation is the process by which reactivated, labile memories are restabilized. Disrupting this process induces retrograde amnesia specific to the reactivated memory, making it a promising therapeutic target for anxiety disorders rooted in maladaptive avoidance. However, the electrophysiological mechanisms underlying reconsolidation are still not fully understood, limiting its translational potential. Here, we show that inducing reconsolidation of a fear-driven avoidance memory in adult male rats increases coherent theta synchrony and directional connectivity between the dorsal CA1 region of the hippocampus and the prelimbic cortex. Optogenetic silencing of dorsal CA1 terminals in the prelimbic cortex during the reconsolidation induction window disrupted this theta coupling and led to delayed memory impairment. These findings demonstrate that reconsolidation depends on theta-mediated information transfer through the direct dorsal CA1-prelimbic pathway and suggest that monitoring or modulating this activity could inform the development of targeted interventions aimed to modify or disrupt distressing, intrusive memories
Avaliação da eficácia de dois programas de leitura dialógica na compreensão de crianças com transtorno do espectro do autismo e desenvolvimento típico
(2025) Walter, Elizabeth Cynthia; Pereira, Rodrigo Neves Romcy; Nunes, Débora Regina de Paula
Prejuízos na linguagem e na compreensão leitora de crianças com desenvolvimento típico (DT) e com transtorno do espectro do autismo (TEA) podem ser minimizados por práticas precoces de leitura. Assim, o objetivo deste estudo foi analisar a eficácia de dois programas de leitura, Reading to Engage Children with Autism in Language and Learning (Recall) e Leitura Dialógica Simples (LDS), implementados em dois pré-escolares com TEA e um com DT. Um delineamento experimental randomizado do tipo ABAB foi empregado para avaliar os efeitos dos dois programas na frequência de respostas corretas a perguntas factuais e inferenciais sobre as histórias narradas, assim como na aprendizagem de vocabulário das três crianças. Os resultados mostram que, por meio da autoscopia e de estratégias de modelação, os sete mediadores, pais das crianças e profissionais de saúde e educação, desenvolveram competências para implementar ambos os protocolos com adequado grau de fidedignidade. As três crianças aprenderam novos vocábulos quando expostas ao Recall e à LDS, sem apresentarem diferenças significativas entre os programas. Em contrapartida, ao avaliarmos a frequência de respostas corretas para o conjunto de tipo de pergunta, observou-se desempenho significativamente melhor para as três crianças com o Recall. Ao estendermos as análises considerando o valor das respostas segundo o nível de ajuda, verificou-se diferença significativa apenas para duas delas. Contribuições e limitações do estudo também são discutidas
Capoeira and brain function: hypotheses and perspectives from a systematic review
(Elsevier BV, 2025-03) Monteiro Junior, Renato Sobral; Fernandes, Valter da Rocha; Oliva, Henrique Nunes Pereira; Prudente, Tiago Paiva; Ribeiro, Sidarta Tollendal Gomes
To review the literature on brain activation and cognitive network in individuals involved in Capoeira. Additionally, we propose a hypothetical model of brain function in response to Capoeira stimuli. Methods: This systematic review was conducted based on PRISMA guidelines. Articles investigating neurocognitive domains or neurophysiological mechanisms in the brains of individuals involved with Capoeira were retrieved from PubMed, Web of Science, Scopus, Embase, and Lilacs in July 2024 (PROSPERO CRD42024556159). Outcomes related to neurocognitive domains or brain functionality, such as cortical and subcortical activity, neural circuitry, and oxygen or glucose metabolism, were analyzed. Results: Five articles with a total of 1,365 individuals involved with Capoeira were selected and analyzed. Individuals involved with Capoeira presented alterations in the left hemisphere of the precentral gyrus, the right dorsal premotor cortex, posterior insular cortex, visual cortex, supplementary motor area, and post-central gyrus, among other subregions. Neurocognitive effects were particularly prominent in children. Conclusion: Capoeira practice engages a broad network of brain regions, notably the prefrontal, temporal, and parietal cortices, regions related to motor and cognitive processing. Subcortical regions also seem to be activated in individuals involved in Capoeira, potentially relating to executive control and emotions. This review highlights the neural engagement related to Capoeira exposure, suggesting benefits in motor, cognitive, and emotional processing, which may inspire future research and therapeutic applications of Capoeira
NEIL3 influences adult neurogenesis and behavioral pattern separation via WNT signaling
(Springer Science and Business Media LLC, 2025-03) Fernandez-Berrocal, Marion S.; Reis, Amilcar; Rolseth, Veslemøy; Suganthan, Rajikala; Kuśnierczyk, Anna; França, Arthur; Soares, Annara Yve Moura; Kunath, Nicolas; Bugaj, Anna M.; Abentung, Andreas; Eide, Lars; Leao, Richardson Naves; Bjørås, Magnar; Scheffler, Katja; Ye, Jing
Adult neurogenesis in the hippocampus, involving the generation and integration of new neurons, is essential for behavioral pattern separation, which supports accurate memory recall and cognitive plasticity. Here, we explore the role of the DNA repair protein NEIL3 in adult hippocampal neurogenesis and behavioral pattern separation. NEIL3 is required for efficient proliferation and neuronal differentiation of neonatal NSPCs and adult-born NPCs in the hippocampus following a behavioral pattern separation task. NEIL3-depleted mice exhibited a reduced preference for the novel object location, indicating a deficit in pattern separation. NEIL3-deficient adult-born neurons exhibited a significant reduction in mature-like membrane properties, indicating impaired functional maturation. Interestingly, these impairments were not associated with the decreased genomic integrity but with the altered transcriptional regulation of the Wnt signaling pathway. Given the importance of adult neurogenesis in cognitive function, targeting NEIL3 could offer therapeutic potential for addressing age-related hippocampal dysfunction and cognitive decline
Sex steroids and brain-derived neurotrophic factor interactions in the nervous system: a comprehensive review of scientific data
(MDPI AG, 2025-03) Assis, Gilmara Gomes de; Sousa, Maria Bernardete Cordeiro de; Murawska-Ciałowicz, Eugenia
Sex steroids and the neurotrophin brain-derived neurotrophic factor (BDNF) participate in neural tissue formation, phenotypic differentiation, and neuroplasticity. These processes are essential for the health and maintenance of the central nervous system. Aim: The aim of our review is to elucidate the interaction mechanisms between BDNF and sex steroids in neuronal function. Method: A series of searches were performed using Mesh terms for androgen/receptors, estrogen/receptors, and BDNF/receptors, and a collection of the scientific data available on PubMed up to February 2025 about mechanical interactions between BDNF and sex steroids was included in this literature review. Discussion: This review discussed the influence of sex steroids on the formation and/or maintenance of neural circuits via different mechanisms, including the regulation of BDNF expression and signaling. Estrogens exert a time- and region-specific effect on BDNF synthesis. The nuclear estrogen receptor can directly regulate BDNF expression, independently of the presence of estrogen, in neuronal cells, whereas progesterone and testosterone upregulate BDNF expression via their specific nuclear receptors. In addition, testosterone has a positive effect on BDNF release by glial cells, which lack androgen receptors
Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review
(Springer Science and Business Media LLC, 2024-12) Cruz, Rafael Vitor Lima da; Leao, Richardson Naves; Moulin, Thiago Cordeiro
In the mammalian brain, new neurons continue to be generated throughout life in a process known as adult neurogenesis. The role of adult-generated neurons has been broadly studied across laboratories, and mounting evidence suggests a strong link to the HPA axis and concomitant dysregulations in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, cannabinoids, and a variety of ever-growing chemical categories, have emerged as therapeutic options for neuropsychiatric disorders, while numerous reports link their effects to increased adult neurogenesis. In this systematic review, we examine studies assessing neurogenesis or other neurogenesis-associated brain plasticity after psychedelic interventions and aim to provide a comprehensive picture of how this vast category of compounds regulates the generation of new neurons. We conducted a literature search on PubMed and Science Direct databases, considering all articles published until January 31, 2023, and selected articles containing both the words “neurogenesis” and “psychedelics”. We analyzed experimental studies using either in vivo or in vitro models, employing classical or atypical psychedelics at all ontogenetic windows, as well as human studies referring to neurogenesis-associated plasticity. Our findings were divided into five main categories of psychedelics: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. We described the outcomes of neurogenesis assessments and investigated related results on the effects of psychedelics on brain plasticity and behavior within our sample. In summary, this review presents an extensive study into how different psychedelics may affect the birth of new neurons and other brain-related processes. Such knowledge may be valuable for future research on novel therapeutic strategies for neuropsychiatric disorders
Fecal steroids of breeding and non-breeding free-ranging black-tufted marmoset females
(FapUNIFESP (SciELO), 2024) Silva, Ita de Oliveira e; Boere, Vanner; Sousa, Maria Bernardete Cordeiro de
The relationships between members of the groups include behaviors related to affiliation, dispute for dominant positions, parental care, and facing disputes for food and territory. All these activities are under hormone modulation and those of a steroidal nature are heavily involved. Despite this, only few data are available on steroid hormones in free-ranging marmosets of the Callithrix genus, which limits the understanding of the physiological functioning and modulation of the socio-sexual behavior by steroid hormones of this taxon. In this study, we characterized fecal concentrations of progesterone, estrogens, and glucocorticoids of six breeding and non-breeding females from two groups of free-ranging Callithrix penicillata (É. Geoffroy, 1812). The concentration of progesterone was significantly higher in females which gave birth, compared to non-breeding females. The levels of fecal estrogens and glucocorticoids did not differ between breeding and non-breeding females. The data are in agreement with the few studies on steroid values of wild and captive marmosets. This study shows the concentrations of progesterone and glucocorticoids in free-ranging C. penicillata for the first time, and it is the only study reporting the concentration of fecal estrogens in wild marmosets. Overall, the high levels of progesterone associated with pregnancy in free-ranging C. penicillata as well as levels of estrogens and glucocorticoids close to those reported for other species, suggest a conserved pattern of hormonal secretion between Callithrix species that have been studied in captivity
Unraveling the protective genetic architecture of COVID-19 in the Brazilian Amazon
(Springer Science and Business Media LLC, 2024-11) Barros, Maria Clara; Souza, Jorge Estefano Santana de; Gomes, Daniel Henrique Ferreira; Pinho, Catarina Torres; Silva, Caio Santos; Silva, Cintia Helena Braga da; Cavalcante, Giovanna Chaves; Magalhães, Leandro; Pinheiro, Jhully Azevedo dos Santos; Quaresma, Juarez Antônio Simões; Falcão, Luiz Fábio Magno; Costa, Patrícia Fagundes; Salgado, Cláudio Guedes; Carneiro, Thiago Xavier; Burbano, Rommel Rodrigues; Vieira, José Ricardo dos Santos; Santos, Sidney; Souza, Giordano Bruno Soares; Souza, Sandro José de; Santos, Andrea Kely Campos Ribeiro dos
Despite all the efforts acquired in four years of the COVID-19 pandemic, the path to a full understanding of the biological mechanisms involved in this disease remains complex. This is partly due to a combination of factors, including the inherent characteristics of the infection, socio-environmental elements, and the variations observed within both the viral and the human genomes. Thus, this study aimed to investigate the correlation between genetic host factors and the severity of COVID-19. We conducted whole exome sequencing (WES) of 124 patients, categorized into severe and non-severe groups. From the whole exome sequencing (WES) association analysis, four variants (rs1770731 in CRYBG1, rs7221209 in DNAH17, rs3826295 in DGKE, and rs7913626 in CFAP46) were identified as potentially linked to a protective effect against the clinical severity of COVID-19, which may explain the less severe impact of COVID-19 on the Northern Region. Our findings underscore the importance of carrying out more genomic studies in populations living in the Amazon, one of the most diverse from the point of view of the presence of rare and specific alleles. To our knowledge, this is the first WES study of admixed individuals from the Brazilian Amazon to investigate genomic variants associated with the clinical severity of COVID-19
Severe toxicities in amazonian populations and the role of precision medicine in acute lymphoblastic leukemia treatment
(Springer Science and Business Media LLC, 2024-11) Leitão, Luciana Pereira Colares; Monte, Natasha; Rodrigues, Juliana Carla Gomes; Freitas, Lilian Marques de; Santos, André Mauricio Ribeiro dos; Santos, Andrea Kely Campos Ribeiro dos; Santos, Sidney; Souza, Sandro José de; Fernandes, Marianne Rodrigues; Santos, Ney Pereira Carneiro dos
Corticosteroids, such as prednisone or dexamethasone, constitute integral components of antineoplastic regimens for Acute Lymphoblastic Leukemia (ALL) therapy, albeit accompanied by significant adverse effects. The multifactorial nature of interindividual variability in drug response, encompassing genetic polymorphisms, underscores the complexity of pharmacotherapy outcomes. However, pharmacogenetic investigations hitherto have predominantly focused on cohorts of European and North American descent, thus limiting the generalizability of findings to populations with minimal representation. Indigenous populations in Brazil, particularly those inhabiting the Amazon region, exhibit a distinctive genetic heritage, predominantly characterized by Native American ancestry. These populations frequently manifest suboptimal therapeutic responses and elevated mortality rates following ALL treatment. Therefore, delineating the molecular signatures of genes implicated in the corticosteroid pathway within these indigenous cohorts assumes paramount importance. This study identified novel variants within genes associated with the glucocorticoid pathway in indigenous Amazonian populations and conducted comparative analyses of variant frequencies across diverse global populations. The findings underscore the genetic uniqueness of indigenous groups and highlight the potential impact of genetic factors on adverse responses to ALL treatment. Precision medicine approaches tailored to the genetic peculiarities of indigenous populations emerge as imperative strategies for optimizing therapeutic efficacy and mitigating treatment-related toxicities in these communities
Interleukin-12 modulates sleep–wake activity and improves performance in a memory task
(Springer Science and Business Media LLC, 2024-11) Esumi, Lia Assae; Queiroz, Claudio Marcos Teixeira de; Ribeiro, Daniel Araki; Hipólide, Débora Cristina
Background: Cytokines, known for their pro- and anti-inflammatory roles, are also key regulators of sleep–wake cycles. Classical pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), are associated with increased sleep, particularly slow-wave sleep (SWS), while anti-inflammatory cytokines, like interleukin-10 (IL-10), generally reduce sleep duration. Given the essential role of sleep in memory consolidation, this study aimed to investigate whether interleukin-12 (IL-12), a pro-inflammatory cytokine, could increase sleep duration following a memory acquisition task and subsequently improve memory performance. Male Swiss mice were surgically implanted with electrodes for electrocorticogram (ECoG) and electromyogram (EMG) recordings to track their sleep–wake cycles. After a recovery period, baseline sleep–wake activity was recorded. The mice were then randomly assigned to two groups and treated with either IL-12 (0.5 µg, i.p.) or a phosphate-buffered saline (PBS, i.p.) control, administered immediately before the multiple-trial inhibitory avoidance (MTIA) task, a behavioral test used to assess memory performance. Following the memory acquisition session, sleep–wake activity was immediately recorded for a continuous 24-h period. Results: Mice treated with IL-12 exhibited longer latency to cross into the dark compartment during the MTIA test, indicating improved memory retention compared to the control group. Interestingly, this improved performance was associated with prolonged wakefulness, particularly in the first three hours after task acquisition. Conclusion: The study shows that IL-12 can improve memory retention through prolonged wake episodes rather than increased sleep. This finding challenges the conventional understanding that sleep is the primary state for memory consolidation, suggesting that under specific conditions, wakefulness may also play a key role in supporting memory processes. Further research is needed to explore the underlying mechanisms of IL-12's cognitive effects
Communication subspace dynamics of the canonical olfactory pathway
(2024-12) Gonzalez, Joaquín; Torterolo, Pablo; Bolding, Kevin A.; Tort, Adriano Bretanha Lopes
Understanding how different brain areas communicate is crucial for elucidating the mechanisms underlying cognition. A possible way for neural populations to interact is through a communication subspace, a specific region in the state-space enabling the transmission of behaviorally relevant spiking patterns. In the olfactory system, it remains unclear if different populations employ such a mechanism. Our study reveals that neuronal ensembles in the main olfactory pathway (olfactory bulb to olfactory cortex) interact through a communication subspace, which is driven by nasal respiration and allows feedforward and feedback transmission to occur segregated along the sniffing cycle. Moreover, our results demonstrate that subspace communication depends causally on the activity of both areas, is hindered during anesthesia, and transmits a low-dimensional representation of odor
SSVEP modulation via non-volitional neurofeedback: an in silico proof of concept
(IOP Publishing, 2024-11) Estiveira, João; Soares, Ernesto; Pires, Gabriel; Nunes, Urbano J.; Sousa, Teresa; Ribeiro, Sidarta Tollendal Gomes; Castelo-Branco, Miguel
Objective Neuronal oscillatory patterns are believed to underpin multiple cognitive mechanisms. Accordingly, compromised oscillatory dynamics were shown to be associated with neuropsychiatric conditions. Therefore, the possibility of modulating, or controlling, oscillatory components of brain activity as a therapeutic approach has emerged. Typical non-invasive brain-computer interfaces (BCI) based on EEG have been used to decode volitional motor brain signals for interaction with external devices. Here we aimed at feedback through visual stimulation which returns directly back to the visual cortex. Approach Our architecture permits the implementation of feedback control-loops capable of controlling, or at least modulating, visual cortical activity. As this type of neurofeedback depends on early visual cortical activity, mainly driven by external stimulation it is called non-volitional or implicit neurofeedback. Because retino-cortical 40-100ms delays in the feedback loop severely degrade controller performance, we implemented a predictive control system, called a Smith-Predictor (SP) controller, which compensates for fixed delays in the control loop by building an internal model of the system to be controlled, in this case the EEG response to stimuli in the visual cortex. Main Results Response models were obtained by analyzing, EEG data (n=8) of experiments using periodically inverting stimuli causing prominent parieto-occipital oscillations, the Steady-State Visual Evoked Potentials (SSVEPs). Averaged subject-specific SSVEPs, and associated retina-cortical delays, were subsequently used to obtain the SP controler's Linear, Time-Invariant (LTI) models of individual responses. The SSVEP models were first successfully validated against the experimental data. When placed in closed loop with the designed SP controller configuration, the SSVEP amplitude level oscillated around several reference values, accounting for inter-individual variability. Significance In silico and in vivo data matched, suggesting model's robustness, paving the way for the experimental validation of this non-volitional neurofeedback system to control the amplitude of abnormal brain oscillations in autism and attention and hyperactivity deficits
Physical fitness, executive functions, and academic performance in children and youth: a cross-sectional study
(MDPI AG, 2024-11) Fernandes, Valter; Silva, Arthur; Carvalho, Andrea; Ribeiro, Sidarta Tollendal Gomes; Deslandes, Andrea
The aim of this cross-sectional study was to investigate the relationship between physical fitness, executive function, and academic performance in children and adolescents. A total of 131 students (49% female) aged 10–15 years from a public school in Rio de Janeiro were assessed in executive functions (hearts and flowers, Corsi’s block, and digit span tasks), academic performance (Portuguese, reading, math, and overall school grade), physical tests (touch test disc, agility, lower limb and upper limb explosive strength), and anthropometric measurements. Regression results showed that the composite of sports-related fitness measures was the best predictor of executive functions (β = 0.472; t = −6.075 p < 0.001). Decision tree classifier analysis showed that the combination of factors that discriminated better and worse executive function groups were better performance in hand–eye coordination (TTD), math, and upper limb strength (ULEST). Sports-related fitness is significantly correlated with executive function. Hand–eye motor coordination has been identified as the most important predictor of improved cognitive outcomes, surpassing even academic skills. These findings should be considered in the design of physical activity programs in school settings, which may have a positive impact on child development, reflected in the reduction of academic and socioeconomic disparities
Active sampling as an information seeking strategy in primate vocal interactions
(Springer Science and Business Media LLC, 2024-09) Varella, Thiago T.; Takahashi, Daniel Yasumasa; Ghazanfar, Asif A.
Active sensing is a behavioral strategy for exploring the environment. In this study, we show that contact vocal behaviors can be an active sensing mechanism that uses sampling to gain information about the social environment, in particular, the vocal behavior of others. With a focus on the real-time vocal interactions of marmoset monkeys, we contrast active sampling to a vocal accommodation framework in which vocalizations are adjusted simply to maximize responses. We conduct simulations of a vocal accommodation and an active sampling policy and compare them with actual vocal interaction data. Our findings support active sampling as the best model for real-time marmoset monkey vocal exchanges. In some cases, the active sampling model was even able to partially predict the distribution of vocal durations for individuals to approximate the optimal call duration. These results suggest a non-traditional function for primate vocal interactions in which they are used by animals to seek information about their social environments
Brazilian psychedelic science and the frontiers of psychiatry
(2024-10) Araujo, Draulio Barros de; Sanchez, Tiago Arruda; Ribeiro, Sidarta Tollendal Gomes
The use of psychedelic substances has intrigued, benefited, and challenged humanity for millennia. These substances, found regularly in nature, are known to induce non-ordinary states of consciousness. They provide heightened sensory, emotional and cognitive experiences, which include augmented visual imagery, changes in thought, mood, and awareness, perception of space-time and reality and, in many cases, profound insights, and mystical experiences. Throughout history, many indigenous populations around the world developed the use of these substances, especially as a vital component of healing. From the Amazon, for example, Ayahuasca emerged, a drink made from the combination of two plants, used ancestrally by shamans to promote physical and psychological healing. Likewise, indigenous populations in North America, such as the Navajo, retain the ancestral use of the peyote cactus as sacred medicine, while indigenous populations such as the Mazatecs of Mexico used psilocybin-containing mushrooms in their healing rituals
Visual coding along multiple brain areas
(Universidad de San Buenaventura, 2024-10) Xavier, Vitória de Araújo; Melo, Nayara da Silva; Ribeiro, Sidarta Tollendal Gomes; Vasconcelos, Nivaldo Antonio Portela de
This study focuses on understanding visual coding in multiple brain areas and its implications for neural processing in the visual system. It highlights the use of simultaneous recordings of large neuronal populations to investigate how visual information is encoded and processed in the brain. By studying the activity of multiple brain areas, the paper aims to uncover the mechanisms underlying brain-wide visual perception and provide insights into the neural basis of visual processing. The findings of this research contribute to the broader field of neuroscience and have implications for understanding visual disorders and developing therapeutic interventions
It is time for more holistic practices in mental health
(Public Library of Science (PLoS), 2024-06) Ribeiro, Sidarta Tollendal Gomes; Pimentel, Ana Paula; Fernandes, Valter da Rocha; Deslandes, Andrea Camaz; Amarante, Paulo Duarte de Carvalho
Hegemonic psychiatric models in the 20th century, centered on the notion of disease, were willing to consider a single ’natural’ primary cause—either biochemical or neurophysiological–as sufficient explanation for complex psychological and social phenomena like psychosis or depression. The pharmacological treatment of mental health conditions came to be understood solely in terms of metabolic replenishment to fight a putative ’chemical imbalance’, without a true need to delve into the recesses of the patients’ minds and bodies. These overly simplistic models collapsed in the past two decades, and the trend is now the opposite, towards the recognition that mental health conditions are to a large extent, a social construct produced by lifestyles that jeopardize the essential tenets of good health: sleep, nutrition, exercise, introspection, and mind-body connection. Although psychiatric drugs are widely prescribed as ’effective’ treatment, the number of people diagnosed with mental health conditions has increased substantially in the past decades. The World Health Organization (WHO) estimates that the prevalence of mental health conditions has risen from 416 million people in 1990 to over 615 million people in recent years [1]. Similarly, the U.S. National Survey on Drug Use and Health has reported significant increases in rates of depression, anxiety, and suicidal ideation, particularly among young adults, over the past decade [2]. A significant increase in the diagnosis of attention deficit hyperactivity disorder (ADHD) in children has also been reported in the U.S. [3] and other countries. These increases have been attributed to better diagnosis and the increasing prevalence of conditions like anxiety and depression, which likely reflect the negative impact of contemporary lifestyle on mental health. Nevertheless, two other factors often overlooked, may also contribute to explain increase: the iatrogenic effects of psychotropic drugs, and overdiagnosis due to financial conflicts of interest, or prejudice against neurodivergence, as may be the case of ADHD and certain forms of autism
The Alzheimer’s disease risk gene BIN1 regulates activity-dependent gene expression in human-induced glutamatergic neurons
(Springer Science and Business Media LLC, 2024-03) Saha, Orthis; Farias, Ana Raquel Melo de; Pelletier, Alexandre; Siedlecki-Wullich, Dolores; Landeira, Bruna Soares; Gadaut, Johanna; Carrier, Arnaud; Vreulx, Anaïs-Camille; Guyot, Karine; Shen, Yun; Bonnefond, Amelie; Amouyel, Philippe; Tcw, Julia; Kilinc, Devrim; Queiroz, Claudio Marcos Teixeira de; Delahaye, Fabien; Lambert, Jean-Charles; Costa, Marcos Romualdo
Bridging Integrator 1 (BIN1) is the second most important Alzheimer’s disease (AD) risk gene, but its physiological roles in neurons and its contribution to brain pathology remain largely elusive. In this work, we show that BIN1 plays a critical role in the regulation of calcium homeostasis, electrical activity, and gene expression of glutamatergic neurons. Using single-cell RNA-sequencing on cerebral organoids generated from isogenic BIN1 wild type (WT), heterozygous (HET) and homozygous knockout (KO) human-induced pluripotent stem cells (hiPSCs), we show that BIN1 is mainly expressed by oligodendrocytes and glutamatergic neurons, like in the human brain. Both BIN1 HET and KO cerebral organoids show specific transcriptional alterations, mainly associated with ion transport and synapses in glutamatergic neurons. We then demonstrate that BIN1 cell-autonomously regulates gene expression in glutamatergic neurons by using a novel protocol to generate pure culture of hiPSC-derived induced neurons (hiNs). Using this system, we also show that BIN1 plays a key role in the regulation of neuronal calcium transients and electrical activity via its interaction with the L-type voltage-gated calcium channel Cav1.2. BIN1 KO hiNs show reduced activity-dependent internalization and higher Cav1.2 expression compared to WT hiNs. Pharmacological blocking of this channel with clinically relevant doses of nifedipine, a calcium channel blocker, partly rescues electrical and gene expression alterations in BIN1 KO glutamatergic neurons. Further, we show that transcriptional alterations in BIN1 KO hiNs that affect biological processes related to calcium homeostasis are also present in glutamatergic neurons of the human brain at late stages of AD pathology. Together, these findings suggest that BIN1-dependent alterations in neuronal properties could contribute to AD pathophysiology and that treatment with low doses of clinically approved calcium blockers should be considered as an option to slow disease-onset and progression
5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats
(Springer Science and Business Media LLC, 2024-05) Souza, Annie da Costa; Souza, Bryan da Costa; França, Arthur Sergio Cavalcanti de; Moradi, Marzieh; Souza, Nicholy C.; Leão, Emelie Katarina Svahn; Tort, Adriano Bretanha Lopes; Leao, Richardson Naves; Santos, Vítor Lopes dos; Ribeiro, Sidarta Tollendal Gomes
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs
Molecular profile of variants potentially associated with severe forms of COVID-19 in Amazonian indigenous populations
(MDPI AG, 2024-02) Coelho, Rita de Cássia Calderaro; Martins, Carlliane Lima e Lins Pinto; Pastana, Lucas Favacho; Rodrigues, Juliana Carla Gomes; Aguiar, Kaio Evandro Cardoso; Paes, Amanda de Nazaré Cohen; Gellen, Laura Patrícia Albarello; Moraes, Francisco Cezar Aquino de; Calderaro, Maria Clara Leite; Assunção, Letícia Almeida de; Silva, Natasha Monte da; Pereira, Esdras Edgar Batista; Santos, André Mauricio Ribeiro dos; Santos, Andrea Kely Campos Ribeiro dos; Burbano, Rommel Mario Rodriguez; Souza, Sandro José de; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Santos, Sidney Emanuel Batista dos; Fernandes, Marianne Rodrigues; Santos, Ney Pereira Carneiro dos
Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2. Genome-wide association studies (GWASs) have suggested a strong association of genetic factors with the severity of the disease. However, many of these studies have been completed in European populations, and little is known about the genetic variability of indigenous peoples’ underlying infection by SARS-CoV-2. The objective of the study is to investigate genetic variants present in the genes AQP3, ARHGAP27, ELF5L, IFNAR2, LIMD1, OAS1 and UPK1A, selected due to their association with the severity of COVID-19, in a sample of indigenous people from the Brazilian Amazon in order to describe potential new and already studied variants. We performed the complete sequencing of the exome of 64 healthy indigenous people from the Brazilian Amazon. The allele frequency data of the population were compared with data from other continental populations. A total of 66 variants present in the seven genes studied were identified, including a variant with a high impact on the ARHGAP27 gene (rs201721078) and three new variants located in the Amazon Indigenous populations (INDG) present in the AQP3, IFNAR2 and LIMD1 genes, with low, moderate and modifier impact, respectively

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