Investigating Morphological Changes of the Hippocampus After Prolonged Aerobic Exercise in Mice: Neural Function and Learning Capabilities / Investigación de los Cambios Morfológicos del Hipocampo Después De un Ejercicio Aeróbico Prolongado en Ratones: Función Neuronal y Capacidades de Aprendizaje

SUMMARY: Both the academic and popular worlds have paid close attention to the link between exercise and cognitive performance. It is increasingly important to understand the numerous mechanisms by which exercise might influence cognitive abilities in view of the continuous societal issues caused by aging populations and the prevalence of disorders associated to cognitive decline. A rising amount of evidence showing a favorable association between physical activity and cognitive well-being serves as the foundation for the justification for studying the effects of exercise on cognitive function and learning ability. The study employed an 8-week treadmill based on exercise on male adults C57BL/6 mice. The exercise group were engaged in 5 sessions a week gradually increasing the intensity of the protocol by 5 % each week. The Mice cognitive assessments were done using Morris Water Maze and Novel Object Recognition tests. The long term-impact on learning ability were further assessed through immmohistochemistry and molecular analysis of the hippocampal and prefrontal cortex tissues of the animals' brain tissues. The findings showed improved spatial learning abilities, recognition memory, and heighted synaptic plasticity indicated by elevated synaptic makers. The study underscores the role of long-term aerobic exercise in augmenting cognitive performance. It not only contributes to the understanding of the interplay between neuroplasticity and cognitive benefits but also the growing body of research on the impact of exercise on cognitive function.

Tanto el mundo académico como el popular han prestado mucha atención al vínculo entre el ejercicio y el rendimiento cognitivo. Es cada vez más importante comprender los numerosos mecanismos por los cuales el ejercicio podría influir en las capacidades cognitivas en vista de los continuos problemas sociales causados por el envejecimiento de la población y la prevalencia de trastornos asociados al deterioro cognitivo. Una cantidad cada vez mayor de evidencia que muestra una asociación favorable entre la actividad física y el bienestar cognitivo sirve como base para justificar el estudio de los efectos del ejercicio sobre la función cognitiva y la capacidad de aprendizaje. El estudio se realizó en ratones machos adultos C57BL/6 utilizándose en los ejercicios una cinta rodante durante 8 semanas. El grupo de ejercicio realizó 5 sesiones por semana aumentando gradualmente la intensidad del protocolo en un 5 % cada semana. Las evaluaciones cognitivas de los ratones se realizaron utilizando las pruebas Morris Water Maze y Novel Object Recognition. El impacto a largo plazo en la capacidad de aprendizaje se evaluó mediante inmunohistoquímica y análisis molecular de los tejidos del hipocampo y la corteza prefrontal de los tejidos cerebrales de los animales. Los hallazgos mostraron mejoras en las habilidades de aprendizaje espacial, la memoria de reconocimiento y una mayor plasticidad sináptica indicada por unos creadores sinápticos elevados. El estudio subraya el papel del ejercicio aeróbico a largo plazo para aumentar el rendimiento cognitivo. No sólo contribuye a la comprensión de la interacción entre la neuroplasticidad y los beneficios cognitivos, sino también al creciente conjunto de investigaciones sobre el impacto del ejercicio en la función cognitiva.

Acteoside Attenuates Recognition Memory Impairment in CUMS Rats via Regulating Synaptic Plasticity and mTOR Signaling Pathway / El Acteoside Atenúa el Deterioro de la Memoria de Reconocimiento en Ratas ELCI Mediante la Regulación de la Plasticidad Sináptica y la Vía de Señalización mTOR

SUMMARY: We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and p- P70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression.

Evaluamos el papel y el mecanismo del acteoside en la regulación del deterioro de la memoria inducido por estrés leve crónico impredecible (ELCI). Se utilizó ELCI para inducir depresión en ratas y el establecimiento exitoso del modelo ELCI se verificó mediante una prueba de natación forzada y una prueba de preferencia de sacarosa. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos evaluaron las funciones de la memoria. Los cambios estructurales en la corteza y el hipocampo se observaron mediante tinción con hematoxilina y eosina (HE). La tinción por inmunofluorescencia y la transferencia Western determinaron los niveles de proteína. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos mostraron que había un deterioro del rendimiento de la memoria en ratas del grupo ELCI, que mejoró con el tratamiento con acteósidos. La tinción con HE mostró que la exposición a ELCI dañó la estructura de la corteza y el hipocampo, mientras que el tratamiento con actósidos alivió los cambios estructurales. En comparación con el grupo de control, los niveles de BNDF y CREB en la corteza y el hipocampo del grupo ELCI disminuyeron significativamente. Acteoside revirtió significativamente las expresiones de estas proteínas en ratas ELCI. Mientras tanto, en comparación con el grupo control, los niveles de p-mTOR y p-P70S6K en la corteza y el hipocampo del grupo ELCI aumentaron significativamente, y estos cambios fueron revertidos significativamente ELCI por el acteoside. Sin embargo, el efecto del acteoside sobre la señalización de mTOR fue notablemente bloqueado por la rapamicina, un inhibidor específico de la señalización de mTOR. El acteoside puede atenuar el deterioro de la memoria y mejorar el daño neuronal y la plasticidad sináptica en ratas con depresión, probablemente mediante la inhibición de la vía de señalización mTOR. Acteoside puede servir como un reactivo novedoso para la prevención de la depresión.

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke / 神经科学通报·英文版

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

The Memory Orchestra: Contribution of Astrocytes / 神经科学通报·英文版

For decades, memory research has centered on the role of neurons, which do not function in isolation. However, astrocytes play important roles in regulating neuronal recruitment and function at the local and network levels, forming the basis for information processing as well as memory formation and storage. In this review, we discuss the role of astrocytes in memory functions and their cellular underpinnings at multiple time points. We summarize important breakthroughs and controversies in the field as well as potential avenues to further illuminate the role of astrocytes in memory processes.

Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats / 中国中药杂志

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity / 中华医学杂志(英文版)

BACKGROUND@#Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity.@*METHODS@#First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells.@*RESULTS@#A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC.@*CONCLUSIONS@#A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

Effect of Suanzaoren Decoction on expression of ionotropic glutamate receptors and synaptic plasticity in hippocampus of anxiety rats / 中国中药杂志

This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P<0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P<0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P<0.01), and significantly increased levels of GABA(P<0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P<0.05, P<0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.

A bio-inspired hierarchical spiking neural network with biological synaptic plasticity for event camera object recognition / 生物医学工程学杂志

With inherent sparse spike-based coding and asynchronous event-driven computation, spiking neural network (SNN) is naturally suitable for processing event stream data of event cameras. In order to improve the feature extraction and classification performance of bio-inspired hierarchical SNNs, in this paper an event camera object recognition system based on biological synaptic plasticity is proposed. In our system input event streams were firstly segmented adaptively using spiking neuron potential to improve computational efficiency of the system. Multi-layer feature learning and classification are implemented by our bio-inspired hierarchical SNN with synaptic plasticity. After Gabor filter-based event-driven convolution layer which extracted primary visual features of event streams, we used a feature learning layer with unsupervised spiking timing dependent plasticity (STDP) rule to help the network extract frequent salient features, and a feature learning layer with reward-modulated STDP rule to help the network learn diagnostic features. The classification accuracies of the network proposed in this paper on the four benchmark event stream datasets were better than the existing bio-inspired hierarchical SNNs. Moreover, our method showed good classification ability for short event stream input data, and was robust to input event stream noise. The results show that our method can improve the feature extraction and classification performance of this kind of SNNs for event camera object recognition.

Relación entre las ciencias básicas y clínicas en la modulación central del dolor / Relationship between basic and clinical sciences in central pain modulation

Esta revisión busca proporcionar a los profesionales de la salud una mayor comprensión del dolor para su actividad clínica-asistencial. Basados en la hipóte-sis de neuroplasticidad presentada inicialmente por Ramón y Cajal y la teoría de la compuerta en la vía dolorosa presentada por Melzack y Wall, se ha ela-borado una revisión bibliográfica con el objetivo de abordar la modulación de la vía nociceptiva desde un punto de vista fisiopatológico. Asimismo, se presen-tan los principales resultados obtenidos durante los últimos años en nuestro laboratorio usando ratas Wistar hembras como modelo de dolor experimental. Finalmente, se describe un circuito original de modu-lación central a nivel del subnúcleo caudal del trigé-mino con una visión integral de los componentes del sistema nociceptivo orofacial, para ayudar al clínico a comprender situaciones de sensibilización central con perpetuación del dolor y cómo paulatinamente el sistema nervioso central pone en marcha un sistema de modulación para adaptarse y alcanzar un estado similar al basal (AU)

This review aims to provide health professionals with a better understanding of pain for their clinical-care activity. Based on the neuroplasticity hypothesis initially presented by Ramón and Cajal, and the gate theory in the pain pathway presented by Melzack and Wall, a literature review has been carried out with the aim of addressing the modulation of the nociceptive pathway from a pathophysiological point of view. The main results obtained in recent years in our laboratory using female Wistar rats as an experimental pain model are also presented. Finally, an original central modulation circuit at the level of the caudal trigeminal subnucleus is described with a comprehensive view of the components of the orofacial nociceptive system, to help the clinician to understand situations of central sensitization with perpetuation of pain and how the central nervous system gradually sets in motion a modulation system to adapt and reach a state similar to the basal one (AU)

Reflexões sobre o trabalho on-line da neuropsicologia infantil numa visão histórico-cultural / Reflections on the online work of child neuropsychology from a cultural-historical perspective / Reflexiones sobre el trabajo online de la neuropsicología infantil desde una perspectiva histórico-cultural

O isolamento social provocado pela pandemia de covid-19 exigiu uma intensificação no estabelecimento de parâmetros para o trabalho do neuropsicólogo com suas especificidades. Assim, o objetivo deste artigo é levantar reflexões sobre a prática neuropsicológica infantil via internet baseada na nossa experiência prática vivenciada no período, relacionando com as referências teóricas da abordagem histórico-cutural e outros trabalhos que discorrem sobre as particularidades dessa modalidade de atendimento. Para isso, foi realizada uma pesquisa bibliográfica em fontes reconhecidas, como SciELO e Google Acadêmico, utilizando-se marcadores como "neuropsicologia on-line" e "teleneuropsicologia", entre outros, em português, inglês e espanhol. Os trabalhos encontrados foram utilizados como fundamento para discutir as ideias aqui apresentadas, a partir da experiência dos autores durante esse período. Considera-se que os neuropsicólogos precisam enfrentar a possível necessidade do trabalho on-line, considerando que as situações vividas durante a pandemia tendem a aumentar a necessidade de avaliações e intervenções neuropsicológicas. Ao mesmo tempo, se prevê que essa via de trabalho deve se intensificar após o isolamento, dentro do que se tem denominado como "o novo normal". Para isso, é essencial que haja esforço por parte da comunidade neuropsicológica para mostrar como essa área de trabalho pode ser útil para crianças, seus pais e professores. Conclui-se que é preciso ter a noção de que nenhuma via ou metodologia de trabalho é absolutamente completa, sendo essencial a instrumentalização das vantagens e desvantagens de todas elas.(AU)

The social isolation caused by the COVID-19 pandemic demanded intensification in the establishment of parameters for the neuropsychologist's work with its specificities. Thus, the aim of this article is to raise reflections on child neuropsychological practice via the internet, based on our practical experience in this period, relating to the theoretical references of the cultural-historical approach and other works that discuss the particularities of this type of care. For this, a bibliographic research was carried out in recognized sources such as SciELO and Google Scholar, using markers such as "online neuropsychology" and teleneuropsychology, among others, in Portuguese, English and Spanish. The works found were used as a basis for discussing the ideas presented here which are based on the authors' experience during this period. It is considered that neuropsychologists need to face the possible need for online work, considering that situations experienced during the pandemic tend to increase the need for neuropsychological assessments and interventions. At the same time, it is expected that this work path should intensify after isolation, within of what has been called "the new normal". For this, an effort by the neuropsychological community is essential to show how this area of work can be useful for children, their parents and teachers. It is concluded that it is necessary to have the notion that no way or work methodology is absolutely complete, being essential the instrumentalization of the advantages and disadvantages of all of them.(AU)

El aislamiento social provocado por la pandemia de Covid-19 exigió una intensificación en el establecimiento de parámetros para el trabajo del neuropsicólogo con sus especificidades. Así, el objetivo de este artículo es plantear reflexiones sobre la práctica neuropsicológica infantil a través de internet, a partir de nuestra experiencia práctica en este período, en relación con los referentes teóricos del enfoque histórico-cultural y otros trabajos que discuten las particularidades de este tipo de cuidado. Para esto, se realizó una investigación bibliográfica en fuentes reconocidas como SciELO y Google Académico, utilizando marcadores como "neuropsicología en línea" y teleneuropsicología, entre otros, en portugués, inglés y español. Los trabajos encontrados sirvieron de base para discutir las ideas aquí presentadas a partir de la experiencia de los autores durante este período. Se considera que los neuropsicólogos necesitan enfrentar la posible necesidad de trabajo en línea, considerando que las situaciones vividas durante la pandemia tienden a incrementar la necesidad de evaluaciones e intervenciones neuropsicológicas. Al mismo tiempo, se espera que esta vía de trabajo se intensifique después del aislamiento, dentro de lo que se ha denominado "la nueva normalidad". Para esto, un esfuerzo de la comunidad neuropsicológica es fundamental para mostrar cómo esta área de trabajo puede ser útil para los niños, sus padres y profesores. Se concluye que es necesario tener la noción de que ninguna vía o metodología de trabajo es absolutamente completa, siendo imprescindible la instrumentalización de las ventajas y desventajas de todas ellas.(AU)

Impacto do metilfenidato no estresse oxidativo e na plasticidade cerebral / Methylphenidate impact on oxidative stress and brain plasticity

Esse estudo avaliou o impacto do tratamento com cloridrato de metilfenidato (MFD) em crianças com Transtorno de Déficit de Atenção e Hiperatividade. O estudo incluiu metodologia variada, contendo estudo de revisão sobre efeito de metilfenidato sobre BDNF e estudo de coorte experimental. O estudo de revisão seguiu as diretrizes do PRISMA e foi registrado no PROSPERO. No estudo experimental, coorte aberta de centro único foi desenhada, com amostra de conveniência recrutada entre os anos de 2020 e 2022, no ambulatório de ensino da faculdade de Medicina da Universidade Federal de Viçosa (MG). Amostra de 62 crianças, 6 a 14 anos incompletos, sem tratamento prévio, diagnosticadas por psiquiatra infantil segundo os critérios do Manual Diagnóstico e Estatístico dos Transtornos Mentais (DSM5). Média de 8 consultas de acompanhamento clínico realizadas, com coletas de amostras biológicas em 3 delas: antes do início do MFD, com 12 e 24 semanas após uso da medicação. Amostra caracterizada quanto a dados sociodemográficos, sintomas de TDAH, avaliações clínica e psiquiátrica e testagem de inteligência pela psicologia. Amostras biológicas para dosagens séricas de marcadores oxidativos (níveis de capacidade antioxidante total -FRAP -, atividade de superóxido dismutase ­ SOD-, catalase ­ CAT -, glutathione -S-transferase -GST-, níveis de peroxidação lipídica e de proteínas carboniladas) foram coletadas de cada criança nos três momentos da avaliação. Metilfenidato de liberação imediata foi administrado na dosagem de média de 0,65mg/kg/dia. Usou-se o teste de Shapiro-Wilk e Kolmogorov-Smirnov para análise de normalidade. Frequências absolutas e relativas foram determinadas para as variáveis numéricas que foram descritas por suas médias e desvios padrões. Para comparações múltiplas dos parâmetros oxidativos foi realizado pós teste paramétrico de Tukey e para as demais variáveis análise de variância ANOVA (f). Análises dos parâmetros oxidativos foram realizadas no programa GraphPad Prism 7.0 (GraphPad Software, Inc. San Diego, CA, USA) e dos dados sociodemográficos e clínicos no software SPSS (versão 23.0 para Windows). Significância estatística foi considerada com p <0.05. Os resultados mostram: Sexo masculino predominante (71%), idade média 8,58 ± 1,91, predominância de apenas um cuidador - mãe e/ou pai biológico como chefe de família e maior frequência de tipo combinado de TDAH. Pressão arterial sistólica, frequência cardíaca e temperatura corporal alterações significativas, porém sem significância clínica. Índice massa corporal com diferença estatística, 37%, 19,3% e 21% das crianças apresentaram IMC acima do esperado para idade na avaliação 1, 2 e 3 respectivamente. Adesão ao tratamento medicamentoso permaneceu acima de 93,5% na 24ª semana. Durante o tratamento: FRAP não se alterou; atividade de SOD reduziu na 12ª semana em comparação à linha de base; atividade de CAT aumento significativo à 24ª em comparação 12ª semana; aumento significativo dos níveis de peroxidação lipídica à 24ª semana em comparação à 12ª semana. Aumento significativo das proteínas carboniladas na linha de base em comparação aos níveis da 12ª e 24ª semanas. O metilfenidato parece influenciar os parâmetros redox de crianças com TDAH, aumentando o estresse oxidativo. Porém, mecanismos cerebrais tamponam e desconhecemos o resultado dessas interações na estrutura cerebral. Níveis de BDNF não foram influenciados significativamente por metilfenidato em crianças com TDAH, quando comparados a controles em nossa metanálise.

This study evaluated the impact of methylphenidate hydrochloride (MFD) treatment (MFD) in children with Attention Deficit Hyperactivity Disorder. The study included varied methodology, including a review study about methylphenidate effects on BDNF and an experimental cohort study. The review study followed the PRISMA guidelines and was registered in PROSPERO. In the experimental study, a single-center open cohort was designed, with a convenience sample recruited between the years 2020 and 2022, at the teaching outpatient clinic of the Faculty of Medicine at Viçosa Federal University (UFV-MG). Sample with 62 children, 6 to 14 years old, without previous treatment, diagnosed by a child psychiatrist according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM5). Eight clinical follow-up visits were carried out, and biological samples were collected in 3 visits: before MFD beginning and after 12- and 24-weeks medication. Sociodemographic data, ADHD symptoms, clinical and psychiatric assessments were performed, as well as intelligence testing by psychology. Biological samples for oxidative markers serum dosages (total antioxidant capacity levels -FRAP -, superoxide dismutase activity - SOD-, catalase - CAT -, glutathione S transferase -GST-, lipid peroxidation and carbonyl proteins levels) were collected of each child in the 3 evaluation moments. Immediate-release methylphenidate was administered at approximately 0.65mg/kg/day. The Shapiro-Wilk and Kolmogorov-Smirnov test was used for normality analysis. Absolute and relative frequencies were used for numeric variables that were described by their means and standard deviations. Tukey's parametric test and variance analysis ANOVA (f) were performed for multiple comparisons in redox parameters and other variables respectively. Redox parameters analysis was performed using GraphPad Prism 7.0 program (GraphPad Software, Inc. San Diego, CA, USA) and other variables using SPSS software (version 23.0 for Windows). Statistical significance was considered at p<0.05. Male was predominant (71%), with a mean age of 8.58 ± 1.91, mother and/or biological father were the householder in most homes. Systolic blood pressure, heart rate and body temperature had significant changes, but without clinical significance. Body mass index showed a statistical difference, with 37%, 19.3% and 21% of the children having a BMI above the expected for their age in assessment 1, 2 and 3 respectively. Combined-ADHD occurred in 58.1% of the children, inattentive in 32.3% and hyperactive/impulsive in 9.7%. Drug treatment adherence was 98.4% (12th week) and 93.5% (24th week). There were no changes in FRAP levels; SOD activity had significant decreased at week 12 compared to baseline activity; CAT activity showed a significant increase at the 24th week compared to 12th week; Significant increase in lipid peroxidation levels at 24th week compared to 12th week. Significant increase in protein carbonyls levels at baseline (before methylphenidate use) compared to levels at 12 and 24 weeks. Methylphenidate can influence the oxidative and antioxidative parameters of ADHD children, increasing oxidative stress. However, buffer brain mechanisms may act and the result of these interactions in brain structure is not completely known. BDNF levels were not significantly affected by methylphenidate treatment in ADHD children and do not differ from controls in our meta-analysis.

Terapia Notch, uma estratégia no tratamento do zumbido / Notch Therapy, a strategy in the treatment of tinnitus

Contexto: A Terapia Notch surgiu como estratégia promissora no controle do zumbido tonal. Trata-se de estratégia que utiliza a plasticidade neural para inibir as frequências laterais àquela do zumbido, equilibrando sinapses excitatórias e inibitórias e, por conseguinte, reduzindo a percepção e incômodo do zumbido. Objetivo: Avaliar a efetividade da Terapia Notch no controle do zumbido tonal. Material e métodos: Trata-se de sinopse baseada em evidências. Procedeu-se à busca por estudos que associavam zumbido e Terapia Notch em quatro bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2022), PubMed (1966-2022), Portal BVS (1982-2022) e Embase (1974- 2022). Dois pesquisadores independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. O desfecho primário de análise envolveu a melhora clínica do zumbido. Resultados: Foram encontradas 538 referências. Seis estudos foram incluídos (n = 233 participantes). Discussão: A literatura apresenta poucos estudos clínicos de avaliação da terapia Notch para zumbido. Trata-se de ensaios clínicos com amostragem reduzida e heterogeneidade alta. Embora o nível de evidência seja ainda muito limitado, todos esses estudos concluem que a terapia Notch pode ser efetiva no controle do zumbido tonal. Conclusões: A terapia Notch pode trazer benefícios no controle do zumbido tonal, mas novos ensaios clínicos de qualidade e bom delineamento são necessários para maior robustez da evidência.

Epistemologia complexa e autismo: novos horizontes / Complex epistemology and autism: new horizons

Trata-se de uma abordagem paradigmática baseada na complexidade dos indivíduos diagnosticados com Transtornos do Espectro Autista (TEA). Ao não separar a cognição da ontogênese dos sujeitos, este projeto de pesquisa assume uma posição complexa, rompendo com posições comportamentais hegemônicas que não atendem às condições biológicas autopoiéticas (autoprodução) dos seres humanos, ignorando também o potencial neuroplasticidade deles ao lidar com os sujeitos autistas com repetições, reforços e outras atitudes mecânicas. A partir da explicação dessa epistemologia, parte-se para a explicitação do arcabouço teórico que sustenta a pesquisa, cujo eixo gira em torno da aprendizagem como experiência pessoal, acoplada à realidade e não à adaptação. Os seres vivos em seu funcionamento mudam continuamente sua estrutura, que é plástica e conservam sua organização, que é autopoiética. Como instrumento de acoplamento, é utilizado um dispositivo de tecnologia touch, o iPad, que garante ao usuário um tipo de interação muito ativo, desencadeando ao mesmo tempo emoções/cognição, bem como o sistema háptico envolvido (toque). Isso pode desencadear mecanismos neurofisiológicos que ajudam as crianças diagnosticadas como autistas a encontrar outras vias neurais que não as comprometidas pela patologia em questão. O artigo apresenta no final breves ilustrações do processo empírico e as transformações desencadeadas nesses sujeito's ao longo do desenvolvimento do projeto. De acordo com a metodologia complexa, os pesquisadores do projeto atuam como parte do sistema observado, dando conta de suas próprias operações com seus sistemas autônomos. Palavras-chave: Educação especial; autopoiesis; autismo; complexidade; neuroplasticidade

Dysfunctional eating behavior in fibromyalgia and its association with serum biomarkers of brain plasticity (BDNF and S100B): an exploratory study

ABSTRACT Objectives: To assess disordered eating, hunger and satiety perceptions in women with fibromyalgia (FM) compared to healthy controls (HC) and their association with biomarkers of brain plasticity (brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B)). Subjects and methods: Cross-sectional exploratory study. The sample included FM (n = 20) and HC (n = 19), matched to age and waist perimeter. Dysfunctional eating was assessed through the Three Factor Eating Questionnaire and Eating Disorders Examination with a questionnaire. Hunger and satiety levels were rated by a Numerical Scale. Serum leptin, S100B and BDNF were analyzed. Results: The MANCOVA analysis showed that the mean of Emotional Eating rates was 30.65% higher in FM compared to HC ( p = 0.015). Eating, shape and weight concerns were 77.77%, 57.14% and 52.22% higher in FM ( p = <0.001) compared to HC, respectively. Moreover, the FM group reported higher scores for feeling of hunger "[5.2 (±2.9) vs. 4.8 (±2.0); p = 0.042] and lower scores for satiety [7.0 (±1.7) vs . 8.3 (±1.0); p = 0.038]. In the FM group, serum BDNF was negatively associated with hunger (r = - 0.52; p = 0.02), while S100B was positively associated with hunger scores (r = 0.463; p = 0.004). Conclusion: The present findings support the hypothesis that the association between FM and obesity can be mediated by a hedonistic pathway. Further research is needed.

Entrenamiento de la memoria de trabajo en la enfermedad vascular cerebral: revisión sistemática / Working Memory Training after cerebrovascular disease: a systematic review / Treinamento Da Memória Operacional Na Doença Cerebrovascular: Revisão Sistemática

Objetivo: mejorar la independencia funcional de los pacientes con enfermedad vascular cerebral (EVC) es uno de los objetivos que se plantean los equipos de rehabilitación física y cognitiva. Uno de los modelos que podría dar respuesta a este objetivo es el entrenamiento cognitivo de la memoria de trabajo (MT). Aunque esta estrategia se viene estudiando desde hace 20 años, aún es necesario realizar un estudio de revisión sistemática que permita conocer con claridad los efectos del entrenamiento cognitivo computarizado de la MT en el funcionamiento de la vida diaria en pacientes con EVC isquémica. Metodología: para ello, se creó una ecuación de búsqueda para aplicar en la base de datos Web of Science (WoS), en el rango temporal desde enero de 2010 a enero de 2019. Posteriormente, se realiza un análisis bibliométrico con el objetivo de identificar los autores y revistas más importantes sobre el tema de investigación. Finalmente, el reporte cronológico identifica la evolución y avances del impacto de los entrenamientos de la memoria de trabajo en la EVC. Resultados: se encontraron tres enfoques relacionados con: efectos de un programa de realidad virtual en las actividades de la vida diaria, efectos del entrenamiento de la MT en la plasticidad cerebral y efectos del entrenamiento cognitivo de la MT en las actividades de la vida diaria. Conclusión: se ha propuesto el desempeño cognitivo como uno de los componentes más importantes del funcionamiento en la vida diaria, particularmente la MT como mediador entre los programas de entrenamiento cognitivo y las habilidades funcionales. Los entrenamientos cognitivos reducen el deterioro cognitivo y el riesgo de demencia. Sin embargo, los beneficios de un entrenamiento cognitivo se limitan a dominios muy similares a los entrenados (transferencia cercana, más que lejana).

Objective: improving functional independence of patients with cerebrovascular disease has become one of the main goals for physical and cognitive rehabilitation teams. A well-known framework that addresses this issue is Working Memory Training. Although this model has been studied for more than twenty years, a systematic review on the effects of Working Memory Training after ischemic stroke and its impact on everyday functioning is still needed. Methodology: thus, a search equation has been proposed on Web of Science database from January 2010 to January 2019. Then, a bibliometric analysis presents the most important authors and journals in the research topic. Finally, a chronological report shows advanced research lines and effects of Working Memory Training in patients with cerebrovascular disease. Results:these findings showed 3 approaches related to the following: effects of virtual reality-based programs on everyday functioning, effects of Working Memory Training on brain plasticity, and effects of Working Memory Training on everyday life. Conclusion: cognitive performance has been proposed to be one of the most important components of functioning in daily life. Working Memory has been shown to strongly mediate between cognitive training and functional abilities. Cognitive training is asso-ciated with less cognitive decline and reduced risk of dementia. However, the benefits from cognitive training may be limited to highly similar domains (close transfer rather than far transfer).

Introdução: melhorar a independência funcional do paciente com doença cerebrovas-cular (DCV) é um dos objetivos traçados pelas equipes de reabilitação física e cognitiva. Um dos modelos que poderia responder a esse objetivo é o treinamento cognitivo da memória de trabalho (MT).Objetivo: embora essa estratégia seja estudada há 20 anos, ainda é necessário realizar um estudo de revisão sistemática que nos permita conhecer claramente os efeitos do treinamento cognitivo computadorizado da MT no funcionamento da vida diária em pacientes com DCV isquêmica.Metodologia: para isso, foi criada uma equação de busca a ser aplicada na base de dados Web of Science (WoS), no período de janeiro de 2010 a janeiro de 2019. Pos-teriormente, é realizada uma análise bibliométrica a fim de identificar os autores mais importantes e periódicos sobre o tema de pesquisa. Por fim, o relatório cronológico identifica a evolução e a evolução do impacto do treino da memória de trabalho no CVS.Resultados: foram encontradas três abordagens relacionadas a: efeitos de um programa de realidade virtual nas atividades da vida diária, efeitos do treinamento da MT na plas-ticidade cerebral e efeitos do treinamento cognitivo da MT nas atividades da vida diária.Conclusão: o desempenho cognitivo tem sido proposto como um dos componentes mais importantes do funcionamento na vida diária, particularmente a MT como media-dor entre programas de treinamento cognitivo e habilidades funcionais. O treinamento cognitivo reduz o declínio cognitivo e o risco de demência. No entanto, os benefícios do treinamento cognitivo são limitados a domínios muito semelhantes aos treinados (transferência próxima, em vez de distante).

Effects of aerobic physical exercise on neuroplasticity after stroke: systematic review / Efeitos do exercício físico aeróbico na neuroplasticidade após o acidente vascular cerebral: revisão sistemática de literatura

ABSTRACT Background: Stroke is among the leading causes of death and disability worldwide. Interventions for stroke rehabilitation aim to minimize sequelae, promote individuals' independence and potentially recover functional damage. The role of aerobic exercise as a facilitator of post-stroke neuroplasticity in humans is still questionable. Objective: To investigate the impact of aerobic exercise on neuroplasticity in patients with stroke sequelae. Methods: A systematic review of randomized clinical trials and crossover studies was performed, with searches for human studies in the following databases: PUBMED, EMBASE, LILACS and PeDRO, only in English, following the PRISMA protocol. The keywords used for selecting articles were defined based on the PICO strategy. Results: This systematic review evaluated the impacts of aerobic exercise on neuroplasticity through assessment of neural networks and neuronal excitability, neurotrophic factors, or cognitive and functional assessment. Studies that evaluated the effects of aerobic exercise on neuroplasticity after stroke measured through functional resonance (fMRI) or cortical excitability have shown divergent results, but aerobic exercise potentially can modify the neural network, as measured through fMRI. Additionally, aerobic exercise combined with cognitive training improves certain cognitive domains linked to motor learning. Studies that involved analysis of neurotrophic factors to assess neuroplasticity had conflicting results. Conclusions: Physical exercise is a therapeutic intervention in rehabilitation programs that, beyond the known benefits relating to physical conditioning, functionality, mood and cardiovascular health, may also potentiate the neuroplasticity process. Neuroplasticity responses seem more robust in moderate to high-intensity exercise training programs, but dose-response heterogeneity and non-uniform neuroplasticity assessments limit generalizability.

RESUMO Antecedentes: O acidente vascular cerebral (AVC) é a segunda causa principal de morte no mundo. Intervenções para reabilitação dos pacientes com AVC visam minimizar sequelas, promover sua independência e potencialmente recuperar danos funcionais. O papel do exercício aeróbico como facilitador da neuroplasticidade pós-AVC em humanos ainda é questionável. Objetivo: Investigar o impacto do exercício aeróbico na neuroplasticidade em pacientes com sequelas de AVC. Métodos: Foi realizada revisão sistemática de literatura, pesquisando nas seguintes bases de dados: PUBMED, EMBASE, LILACS e PeDRO. Foram selecionados trabalhos em língua inglesa, realizados apenas com humanos, seguindo o protocolo PRISMA. As palavras-chave utilizadas para a seleção de artigos foram definidas com base na estratégia PICO. Resultados: Esta revisão sistemática avaliou os impactos do exercício aeróbico na neuroplasticidade através da avaliação das redes neurais e da excitabilidade neuronal, por meio de fatores neurotróficos, por meio da avaliação cognitiva e funcional. Estudos que avaliaram os efeitos do exercício aeróbico sobre neuroplasticidade após o AVC medido através de ressonância funcional ou excitabilidade cortical, são controversos, mas há dados sugerindo uma modificação da rede neural na ressonância funcional após o exercício aeróbico. Há evidências de que, associar exercício aeróbico com treinamento cognitivo melhora certos domínios cognitivos ligados à aprendizagem motora. Estudos que envolveram a análise de fatores neurotróficos, como avaliação da neuroplasticidade, tiveram resultados conflitantes. Conclusões: Exercício aeróbico é uma intervenção terapêutica em programas de reabilitação, pois, além de proporcionar os benefícios no condicionamento físico, funcionalidade, humor e saúde cardiovascular, pode potencializar a neuroplasticidade.