Rescue Of Memory Research Articles

Targeting aberrant glycosylation to modulate microglial response and improve cognition in models of Alzheimer’s disease

Altered glycosylation profiles have been correlated with potential drug targets in various diseases, including Alzheimer’s disease (AD). In this area, the linkage between bisecting N-acetylglucosamine (GlcNAc), a product of N-acetylglucosaminyltransferase III (GnT-III), and AD has been recognized, however, our understanding of the cause and the causative role of this aberrant glycosylation in AD are far from completion. Moreover, the effects and mechanisms of glycosylation-targeting interventions on memory and cognition, and novel targeting strategies are worth further study. Here, we showed the characteristic amyloid pathology-induced and age-related changes of GnT-III, and identified transcription factor 7-like 2 as the key transcription factor responsible for the abnormal expression of GnT-III in AD. Upregulation of GnT-III aggravated cognitive dysfunction and Alzheimer-like pathologies. In contrast, loss of GnT-III could improve cognition and alleviate pathologies. Furthermore, we found that an increase in bisecting GlcNAc modified ICAM-1 resulted in impairment of microglial responses, and genetic inactivation of GnT-III protected against AD mechanistically by blocking the aberrant glycosylation of ICAM-1 and subsequently modulating microglial responses, including microglial motility, phagocytosis ability, homeostatic/reactive state and neuroinflammation. Moreover, by target-based screening of GnT-III inhibitors from FDA-approved drug library, we identified two compounds, regorafenib and dihydroergocristine mesylate, showing pharmacological potential leading to modulation of aberrant glycosylation and microglial responses, and rescue of memory and cognition deficits.

A decolonial look at the past, present and future based on the rescue of memories of visitors to the National History Museum (Rio de Janeiro, Brazil)

History museums can foster discussions about historical contexts and encourage critical reflections on power relations and values that permeate society, helping to overcome historically constructed prejudices. Knowing the audiences, their perceptions, readings and interpretations, allows the adoption of more efficient communication actions between museums and visitors. Thus, in this qualitative research, we aimed to investigate the memories of the experience of five adult visitors at the National Historical Museum, in Rio de Janeiro, Brazil, eight months after the visit with their families. The methodology involved the use of a semi-structured interview, with the adoption of the stimulated memory method. The results showed that the exhibition was able to promote long-term impacts, enabling the formation of memorable experiences that favored critical reflections on the part of visitors, mainly on the enslavement of black African populations, slave trade and themes related to the period of the Empire, which still reflect its problems today. It is important for museums to approach historical processes, carrying out adequate contextualization, from a decolonial perspective, which serve to raise awareness, educate and promote a movement to repair and correct the hegemonic narratives perpetuated in society.

DNA Methylation Inhibition Reversibly Impairs the Long-Term Context Memory Maintenance in Helix.

This work aims to study the epigenetic mechanisms of regulating long-term context memory in the gastropod mollusk: Helix. We have shown that RG108, an inhibitor of DNA methyltransferase (DNMT), impaired long-term context memory in snails, and this impairment can be reversed within a limited time window: no more than 48 h. Research on the mechanisms through which the long-term context memory impaired by DNMT inhibition could be reinstated demonstrated that this effect depends on several biochemical mechanisms: nitric oxide synthesis, protein synthesis, and activity of the serotonergic system. Memory recovery did not occur if at least one of these mechanisms was impaired. The need for the joint synergic activity of several biochemical systems for a successful memory rescue confirms the assumption that the memory recovery process depends on the process of active reconsolidation, and is not simply a passive weakening of the effect of RG108 over time. Finally, we showed that the reactivation of the impaired memory by RG108, followed by administration of histone deacetylase inhibitor sodium butyrate, led to memory recovery only within a narrow time window: no more than 48 h after memory disruption.

Memory rescue and learning in synaptic impaired neuronal circuits

Neuronal impairment is a characteristic of Alzheimer's disease (AD), but its effect on neural activity dynamics underlying memory deficits is unclear. Here, we studied the effects of synaptic impairment on neural activities associated with memory recall, memory rescue, and learning a new memory, in an integrate-and-fire neuronal network. Our results showed that reducing connectivity decreases the neuronal synchronization of memory neurons and impairs memory recall performance. Although, slow-gamma stimulation rescued memory recall and slow-gamma oscillations, the rescue caused a side effect of activating mixed memories. During the learning of a new memory, reducing connectivity caused impairment in storing the new memory, but did not affect previously stored memories. We also explored the effects of other types of impairments including neuronal loss and excitation-inhibition imbalance and the rescue by general increase of excitability. Our results reveal potential computational mechanisms underlying the memory deficits caused by impairment in AD.

Cultural Heritage and the Base Nacional Comum Curricular: approaches between Heritage Education and the curricular guidelines for Elementary School (Early Years) in the recognition and safeguarding of local culture

This article discusses a possible approach between the debate on identity issues in the expanded field of Cultural Heritage, with Heritage Education as a space for action, and the guidelines on the appreciation of local culture present in the structuring of the Base Nacional Comum Curricular (BNCC) - special attention is devoted to the guidelines of Primary Education – Early Years. The theme can contribute to the construction of critical thinking on citizenship, popular participation, and formation of local identities, considering the relationship between present and past, rescue of memories, feelings of belonging, and identification of cultural references, thus preserving them. Access to the field of heritage ensures educational equity and respect for diversity with theoretical and practical foundations through reflections on Heritage Education, an area of education that must be in constant dialogue due to the experiences and perceptions of educators and students. The article compares the texts present in the BNCC with the theoretical productions on Cultural Heritage and Heritage Education through a literature search, identifying possible paths of educational actions towards inventorying and preserving cultural references of communities located in time and space. It also contributes to a broader discussion on the way Cultural Heritage and Heritage Education are cited in Brazilian official documents via the proposed approach.

Augmenting neurogenesis rescues memory impairments in Alzheimer's disease by restoring the memory-storing neurons.

Hippocampal neurogenesis is impaired in Alzheimer's disease (AD) patients and familial Alzheimer's disease (FAD) mouse models. However, it is unknown whether new neurons play a causative role in memory deficits. Here, we show that immature neurons were actively recruited into the engram following a hippocampus-dependent task. However, their recruitment is severely deficient in FAD. Recruited immature neurons exhibited compromised spine density and altered transcript profile. Targeted augmentation of neurogenesis in FAD mice restored the number of new neurons in the engram, the dendritic spine density, and the transcription signature of both immature and mature neurons, ultimately leading to the rescue of memory. Chemogenetic inactivation of immature neurons following enhanced neurogenesis in AD, reversed mouse performance, and diminished memory. Notably, AD-linked App, ApoE, and Adam10 were of the top differentially expressed genes in the engram. Collectively, these observations suggest that defective neurogenesis contributes to memory failure in AD.

Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke

BackgroundHuman adipose-derived stem cells (hADSCs) have been demonstrated to be a promising autologous stem cell source for treating various neuronal diseases. Our study indicated that hADSCs could be induced into neuron-like cells in a stepwise manner that are characterized by the positive expression of MAP2, SYNAPSIN 1/2, NF-200, and vGLUT and electrophysiological activity. We first primed hADSCs into neuron-like cells (hADSC-NCs) and then intracerebrally transplanted them into MCAO reperfusion mice to further explore their in vivo survival, migration, integration, fate commitment and involvement in neural circuit rebuilding.ResultsThe hADSC-NCs survived well and transformed into MAP2-positive, Iba1- or GFAP-negative cells in vivo while maintaining some proliferative ability, indicated by positive Ki67 staining after 4 weeks. hADSC-NCs could migrate to multiple brain regions, including the cortex, hippocampus, striatum, and hypothalamus, and further differentiate into mature neurons, as confirmed by action potential elicitation and postsynaptic currents. With the aid of a cell suicide system, hADSC-NCs were proven to have functionally integrated into the hippocampal memory circuit, where they contributed to spatial learning and memory rescue, as indicated by LTP improvement and subsequent GCV-induced relapse. In addition to infarction size shrinkage and movement improvement, MCAO-reperfused mice showed bidirectional immune modulation, including inhibition of the local proinflammatory factors IL-1α, IL-1β, IL-2, MIP-1β and promotion proinflammatory IP-10, MCP-1, and enhancement of the anti-inflammatory factors IL-15.ConclusionOverall, hADSC-NCs used as an intermediate autologous cell source for treating stroke can rebuild hippocampus neuronal circuits through cell replacement.

Rational designing of oscillatory rhythmicity for memory rescue in plasticity-impaired learning networks.

In the brain, oscillatory strength embedded in network rhythmicity is important for processing experiences, and this process is disrupted in certain psychiatric disorders. The use of rhythmic network stimuli can change these oscillations and has shown promise in terms of improving cognitive function, although the underlying mechanisms are poorly understood. Here, we combine a two-layer learning model, with experiments involving genetically modified mice, that provides precise control of experience-driven oscillations by manipulating long-term potentiation of excitatory synapses onto inhibitory interneurons (LTPE→I). We find that, in the absence of LTPE→I, impaired network dynamics and memory are rescued by activating inhibitory neurons to augment the power in theta and gamma frequencies, which prevents network overexcitation with less inhibitory rebound. In contrast, increasing either theta or gamma power alone was less effective. Thus, inducing network changes at dual frequencies is involved in memory encoding, indicating a potentially feasible strategy for optimizing network-stimulating therapies.

Educomunicación en la escuela zipaquireña: un lugar para la cultura popular

The school, responding to structured dynamics from stipulated curricula,withdraws into the era of globalization, favoring discourse aimed athomogenizing culture. For this reason, this work sought to generate newspaces within education for the incorporation of popular culture, along withthis, the investigation of identity processes within the Zipaquireñomunicipality (Cundinamarca-Colombia), which after its executionmanaged to find central points in the Zipaquirá of before and the Zipaquiráof now. In this way, guiding both the investigative and pedagogical processfrom the IAP methodology and towards the popular, it was sought to linkPopular Education with modern discourse, seeking the integration ofpolitics (understood from the rescue of memory and the formation of theculture) with education, creating in it a horizontal axis of mainstreamingof higher education and basic education. to link reflective consciousnessfrom there, with spaces for the construction of knowledge experienced andinvestigated by students and the community, in the constant and dialogicalsearch for emancipatory values of the local, the latent, the everyday fromtheir own identity.Key words: social memory, dialogue, social participation, educaciónintercultural, popular culture, educommunication

Study on the state of the art of the “guiding image” – The rescue of a river's memory in favor of an urban river restoration project

The progressive transdisciplinary discussion and the preference for an ecological restoration of degraded water courses over rigid engineering solutions currently influence the urban water management and the construction of a guiding reference image is indispensable for its realization. This review article discusses how this set of goals has been approached, in different fields of knowledge, derived from the term “guiding image”. As part of the technical literature about river restoration, the concept commonly alludes to the rescue of the memory of a river, even if the restoration of the original conditions is not part of the final project goal. This work is part of a larger research on the development of an adequate methodology to leverage the river restoration design, in which natural and urban demands coexist in a resilient state, while the river, as a natural element, has been lost and does not exist in collective memory. The various factors that make up the goals of a project of such complexity made up the questions from which this work was developed. As a result, a systematic literature review was carried out with the support of the free scientific search platform “Google Scholar”. Among the results, nine international theses, two books and seven journal articles were found. The research showed the similarities in the discussions and practices around the world, as well as the continuity of the concepts integrated to the reference image in the restoration project with ecological objectives.

Repeating or spacing learning sessions are strategies for memory improvement with shared molecular and neuronal components.

Intellectual disability is a common feature in genetic disorders with enhanced RAS-ERK1/2 signaling, including neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Additional training trials and additional spacing between trials, respectively, restores memory deficits in animal models of NF1 and NS. However, the relationship between the underlying mechanisms in these strategies remain obscure. Here, we developed an approach to examine the effect of adding training trials or spacing to a weak training protocol and used genetic and behavioral manipulations in Drosophila to explore such question. We found that repetition and spacing effects are highly related, being equally effective to improve memory in control flies and sharing mechanistic bases, including the requirement of RAS activity in mushroom body neurons and protein synthesis dependence. After spacing or repeating learning trials, memory improvement depends on the formation of long-term memory (LTM). Moreover, a disease-related gain-of-function RasV152G allele impaired LTM. Using minimal training protocols, we established that both learning strategies were also equally effective for memory rescue in the RasV152G mutant and showed non-additive interaction of the spacing and repetition effects. Memory improvement was never detected after Ras inhibition. We conclude that memory improvement by spacing or repeating training trials are two ways of using the same molecular resources, including RAS-ERK1/2-dependent signaling. This evidence supports the concept that learning problems in RAS-related disorders depend on the impaired ability to exploit the repetition and the spacing effect required for long-term memory induction.

Sistemática: Implicaciones de la Memoria de Trabajo en el neurodesarrollo y el aprendizaje

The school, responding to structured dynamics from stipulated curricula,withdraws into the era of globalization, favoring discourse aimed athomogenizing culture. For this reason, this work sought to generate newspaces within education for the incorporation of popular culture, along withthis, the investigation of identity processes within the Zipaquireñomunicipality (Cundinamarca-Colombia), which after its executionmanaged to find central points in the Zipaquirá of before and the Zipaquiráof now. In this way, guiding both the investigative and pedagogical processfrom the IAP methodology and towards the popular, it was sought to linkPopular Education with modern discourse, seeking the integration ofpolitics (understood from the rescue of memory and the formation of theculture) with education, creating in it a horizontal axis of mainstreamingof higher education and basic education. to link reflective consciousnessfrom there, with spaces for the construction of knowledge experienced andinvestigated by students and the community, in the constant and dialogicalsearch for emancipatory values of the local, the latent, the everyday fromtheir own identity.Key words: social memory, dialogue, social participation, educaciónintercultural, popular culture, educommunication

Dammarane-type saponins from Gynostemma pentaphyllum and their potential anti-AD activity

To search for potential candidate anti-AD agents, the gypenosideson the aerial parts of Gynostemma pentaphyllum were phytochemically investigated, yielding two undescribed (1-2) and five known (3-7) dammarane saponins. Their molecular structures were unambiguously elucidated via spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, IR, and optical rotation) chemical transformations. All of the compounds possessed a 21-O-n-butyl-20,21-dihydroxy-21,23-epoxydammar-24-ene moiety in their structures.The short-term memory assay on a transgenic fly Alzheimer’s disease (AD) model revealed that all of the compounds displayed potential anti-AD activity. Of the compounds, 1 and 6 at 10 μM showed comparable short-term memory rescue ability to memantine, the positive control, at 100 μM. This study revealed the potent antagonistic effect of dammarane-type saponins 1 and 6 against Alzheimer’s disease.

Deep Brain Stimulation Rescues Memory and Synaptic Activity in a Rat Model of Global Ischemia.

Ischemic stroke is responsible for a large number of neurological deficits including memory impairment. Deep brain stimulation (DBS), a well established therapeutic modality for the treatment of movement disorders, has recently shown potential beneficial effects on memory in animals and patients with Alzheimer's disease. Here, we test DBS for its ability to improve memory impairments by stimulating the entorhinal cortex (EC) in a rat model of global ischemia (GI). Two weeks after GI, adult male rats received high-frequency EC DBS for 1 h, and animals were assessed for changes in locomotor activity, learning, and memory 6 weeks later. GI produced spatial memory impairment that was ameliorated by DBS, with no difference between the group that received DBS for GI (GI-DBS ON group) and nonstroke control groups. Although GI led to a dramatic CA1 neuronal loss that could not be rescued with DBS, stimulation attenuated the reduction of CA1 synaptophysin expression after GI. Further, in vitro slice recordings showed a restoration of typical evoked synaptic dendritic fields in GI-DBS ON animals, indicating that the DBS-induced memory rescue is associated with increased synaptophysin expression and enhanced synaptic function. These results suggest that DBS may ameliorate the functional consequences of cerebral ischemia and point to be a potential new therapeutic approach.SIGNIFICANCE STATEMENT Deep brain stimulation (DBS) is remarkably effective in treating Parkinson's disease and is currently under investigation for the treatment of neuropsychiatric disorders including Alzheimer's disease. Until now, DBS has not been examined for its cognitive benefits in the context of hypoxic-ischemic injuries. Here, we investigated the effect of DBS in a rat model of global ischemia (GI) that mimics the neurological consequences occurring after a cardiac arrest. We show that DBS rescues memory deficits induced by GI and produces changes in synaptic activity in the hippocampus. Novel approaches to improve neurological outcomes after stroke are urgently needed; therefore, the present study highlights a possible role for DBS in the treatment of cognitive impairment associated with ischemia.

SA61 - THE ROLE OF MUSASHI RNA BINDING PROTEINS IN ASSOCIATIVE LEARNING AND MEMORY

Background The Musashi family of RNA binding proteins, MSI-1 and MSI-2, retain a pivotal role in stem cell maintenance, nervous system development and tumourigenesis. Recently, we demonstrated that the C. elegans sole ortholog, MSI-1, can regulate forgetting upon associative learning via a 3’ UTR dependent translational repression of the Arp2/3 actin branching complex. Based on these findings, here we opted to decipher the role of human MSI-1 and MSI-2 in the regulation of associative learning and memory; and investigated whether a conserved mechanism of action exists across species. Methods Based on the homology shared between the human and nematode musashi proteins, we first constructed two transgenic C. elegans lines expressing the human proteins in an msi-1 knockout background by using molecular genetic techniques. Moreover, learning and memory (both short-term and long-term) phenotypes were assessed in a paradigm known as negative olfactory chemotaxis assay. Following, using pharmacological manipulations, the function of human musashi proteins were studied both on the molecular and behavioral level. Results Introduction of both human MSI-1 and MSI-2 proteins fully rescued the previously seen forgetting defect of msi-1 (lf) mutant worms, during C. elegans aversive olfactory short-term and long-term memory. Since musashi was shown to regulate gene expression at the translational level via its highly conserved RRM domain, we next sought to disrupt binding to its downstream targets and assessed the effects at the behavioral level. Pharmacological perturbation of both human MSI-1 and MSI-2 function suppressed the memory rescue phenotype previously observed; without causing locomotion, chemotaxis or learning deficits. Discussion Taken together, our results support a conserved role of musashi in negative associative memory from nematodes to humans and might, ultimately, prove to be helpful in elucidating novel therapy targets for the treatment of memory-related disorders.

La cultura como camino de afirmación, coesión y desarrollo de las geografias de la interioridad en Portugal

This article deals with the question of interiority in Portugal, characterizing one geography that represents almost 2/3 of the country and where only 20% of the population is concentrated. This is a sign of desertification that have resulted from a process of abandonment, isolation, economic disruption and lack of territorial cohesion that have lasted for decades. A new strategy now aims to mobilize public and private actors and stimulate citizenship for one rescue of memory as well to promote the reinforcement of identity and hope in the future. Among other instruments in articulation in the terrain are expected results of one bet in the culture as a way of affirmation, cohesion and development of the interior territory of Portugal.

Phytotherapy in pediatrics: the production of knowledge and practices in Primary Care.

To demonstrate the use of phytotherapy as a therapy adopted in the context of Primary Care to Childhood. Observational and analytical field research, with quantitative-qualitative approach. A semi-structured survey was used on socio-demographic and ethnopharmacological variables, audio interview and daily observation. The production of knowledge about phytotherapy constitutes a family heritage, but incorporated data resulting from the daily experiences shared by the community. The main factors were: easy access to this resource, high costs of conventional treatment, difficulty in accessing medical services and belief in the power of plants. The attributed meanings were: prevention and treatment of injuries, rescue of memory and of experiences, factor integrative with nature and aggregative among members of the community. Rescuing this tradition brings a new meaning to health care.

O marco temporal para demarcação de terras indígenas, memória e esquecimento

Os povos indígenas têm hoje garantido constitucionalmente o direito originário às terras que tradicionalmente ocupam, referendando o instituto do indigenato. No entanto, o Supremo Tribunal Federal vem restringindo esse direito ao estabelecer o chamado marco temporal para demarcação das terras indígenas e, mais recentemente, o Executivo com a aprovação do Parecer da AGU, que pretende vincular toda a Administração Pública Federal a esse entendimento. Essas ações contrariam as conclusões da Comissão Nacional da Verdade, que apontaram um quadro sistemático de remoções forçadas e expulsões em período que antecedeu a Constituição de 1988 e negligenciam os mecanismos transicionais para o restabelecimento da verdade e o resgate da memória, representando a implementação de verdadeira política de esquecimento por parte do Estado brasileiro.

Reconsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens.

Systems consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.

O Projeto Educativo Emancipatório de Boaventura de Sousa Santos e o Resgate Da Memória: Múltiplos Olhares de uma Educação Humanística a partir do Ensino da Ditadura Militar.

Esta pesquisa questiona: Em que medida o desenvolvimento do Projeto Educativo Emancipatório de Boaventura de Sousa Santos e o resgate da memória a partir do ensino da Ditadura Militar, pode contribuir para uma educação humanística? Objetiva-se analisar o ensino da Ditadura Militar na rede pública municipal em Vitória –ES; a relevância do projeto educativo emancipatório de Santos e o resgate da memória na educação e a necessidade do desenvolvimento de um currículo pós crítico para a emancipação do aluno.