scholarly journals A Synaptic Framework for the Persistence of Memory Engrams

2021 ◽  
Vol 13 ◽  
Author(s):  
Priyanka Rao-Ruiz ◽  
Esther Visser ◽  
Miodrag Mitrić ◽  
August B. Smit ◽  
Michel C. van den Oever
Keyword(s):  
Turnover Rate ◽  
Molecular Mechanisms ◽  
Synaptic Proteins ◽  
Synaptic Connectivity ◽  
Cell Network ◽  
New Information ◽  
Memory Persistence ◽  
Continuous Dynamic ◽  
The Brain ◽  
Insight Into

The ability to store and retrieve learned information over prolonged periods of time is an essential and intriguing property of the brain. Insight into the neurobiological mechanisms that underlie memory consolidation is of utmost importance for our understanding of memory persistence and how this is affected in memory disorders. Recent evidence indicates that a given memory is encoded by sparsely distributed neurons that become highly activated during learning, so-called engram cells. Research by us and others confirms the persistent nature of cortical engram cells by showing that these neurons are required for memory expression up to at least 1 month after they were activated during learning. Strengthened synaptic connectivity between engram cells is thought to ensure reactivation of the engram cell network during retrieval. However, given the continuous integration of new information into existing neuronal circuits and the relatively rapid turnover rate of synaptic proteins, it is unclear whether a lasting learning-induced increase in synaptic connectivity is mediated by stable synapses or by continuous dynamic turnover of synapses of the engram cell network. Here, we first discuss evidence for the persistence of engram cells and memory-relevant adaptations in synaptic plasticity, and then propose models of synaptic adaptations and molecular mechanisms that may support memory persistence through the maintenance of enhanced synaptic connectivity within an engram cell network.

scholarly journals Redox and essential metal status in the brain of Wistar rats acutely exposed to a cadmium and lead mixture

2020 ◽  
Vol 71 (3) ◽  
pp. 197-204
Author(s):  
Dragana Javorac ◽  
Aleksandra Buha Đorđević ◽  
Milena Anđelković ◽  
Simona Tatović ◽  
Katarina Baralić ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Real Life ◽  
Thiobarbituric Acid ◽  
Control Group ◽  
Special Importance ◽  
Essential Metal ◽  
Cadmium And Lead ◽  
The Brain ◽  
Insight Into

AbstractMost Pb and Cd neurotoxicity studies investigate exposure to either of the toxic metals alone, while data on co-exposure are scarce. The aim of our study was to fill that gap by investigating acute combined effects of Pb and Cd on redox and essential metal status in the brain of Wistar rats. Animals were randomised in four groups of six to eight rats, which received 15 or 30 mg/kg of Cd, 150 mg/kg of Pb, or 150 mg/kg of Pb + 15 mg/kg of Cd by gavage. The fifth, control, group received distilled water only. Co-treatment with Pb and Cd induced significant increase in malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) compared to control and groups receiving either metal alone. This is of special importance, as MDA presence in the brain has been implicated in many neurodegenerative disorders. The groups did not significantly differ in Zn, Cu, Mn, and Fe brain levels. Our findings highlight the importance of metal mixture studies. Neurotoxicity assessments of single chemicals do not provide a real insight into exposure to mixtures in real life. Further research should look into interactions between these metals to reveal complex molecular mechanisms of their neurotoxicity.

scholarly journals Molekulare Kontrolle der Stabilität und Plastizität von Synapsen

BIOspektrum ◽  
2021 ◽  
Vol 27 (6) ◽  
pp. 588-590
Author(s):  
Zeeshan Mushtaq ◽  
Jan Pielage
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Neurodegenerative Diseases ◽  
Information Flow ◽  
Molecular Mechanisms ◽  
Synaptic Connectivity ◽  
Genetic Mutations ◽  
Neuronal Circuits ◽  
The Brain

AbstractThe precise regulation of synaptic connectivity is essential for the processing of information in the brain. Any aberrant loss of synaptic connectivity due to genetic mutations will disrupt information flow in the nervous system and may represent the underlying cause of psychiatric or neurodegenerative diseases. Therefore, identification of the molecular mechanisms controlling synaptic plasticity and maintenance is essential for our understanding of neuronal circuits in development and disease.

scholarly journals Neuromodulatory connectivity defines the structure of a behavioral neural network

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Feici Diao ◽  
Amicia D Elliott ◽  
Fengqiu Diao ◽  
Sarav Shah ◽  
Benjamin H White
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Synaptic Connectivity ◽  
Behavioral Sequence ◽  
Key Factors ◽  
Functional Architecture ◽  
Network Function ◽  
Input Layer ◽  
The Brain ◽  
Insight Into

Neural networks are typically defined by their synaptic connectivity, yet synaptic wiring diagrams often provide limited insight into network function. This is due partly to the importance of non-synaptic communication by neuromodulators, which can dynamically reconfigure circuit activity to alter its output. Here, we systematically map the patterns of neuromodulatory connectivity in a network that governs a developmentally critical behavioral sequence in Drosophila. This sequence, which mediates pupal ecdysis, is governed by the serial release of several key factors, which act both somatically as hormones and within the brain as neuromodulators. By identifying and characterizing the functions of the neuronal targets of these factors, we find that they define hierarchically organized layers of the network controlling the pupal ecdysis sequence: a modular input layer, an intermediate central pattern generating layer, and a motor output layer. Mapping neuromodulatory connections in this system thus defines the functional architecture of the network.

scholarly journals SYSTEMIC MECHANISMS OF BRAIN REJUVENATION

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 198-198
Author(s):  
Saul Villeda
Keyword(s):  
Molecular Mechanisms ◽  
Circulatory System ◽  
Adult Brain ◽  
Aging Brain ◽  
Aging Effects ◽  
Mechanistic Insight ◽  
Age Related ◽  
The Brain ◽  
Insight Into ◽  
Aging Factors

Abstract Aging drives cellular and cognitive impairments in the adult brain. It is imperative to gain mechanistic insight into what drives aging phenotypes in the brain in order to maintain, and even restore, functional integrity in the elderly. We, and others, have shown that systemic manipulations - such as heterochronic parabiosis (in which a young and old circulatory system are joined) and administration of young blood or exercise induced blood factors - can reverse age-related impairments in regenerative, synaptic and inflammatory processes, as well as rescue cognitive faculties in the aged brain. These studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating pro-youthful factors in young blood elicit rejuvenation while pro-aging factors in old blood drive aging. It has been proposed that introducing pro-youthful factors or mitigating the effect of pro-aging factors may provide effective strategies to rejuvenate aging phenotypes in the brain. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating pro-youthful and pro-aging effects of blood-borne factors. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting rejuvenation in the aging brain.

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

2021 ◽  
Vol 22 (8) ◽  
pp. 4209
Author(s):  
Karolina Kot ◽  
Natalia Łanocha-Arendarczyk ◽  
Michał Ptak ◽  
Aleksandra Łanocha ◽  
Elżbieta Kalisińska ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Therapeutic Interventions ◽  
Parasitic Infections ◽  
Injury Mechanisms ◽  
Kidney Involvement ◽  
Leishmania Spp ◽  
Apoptosis Process ◽  
Insight Into

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.

scholarly journals Molecular mechanisms of metabotropic GABAB receptor function

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3362
Author(s):  
Hamidreza Shaye ◽  
Benjamin Stauch ◽  
Cornelius Gati ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Neurological Diseases ◽  
Activation Mechanism ◽  
Allosteric Modulators ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Drugs ◽  
G Protein Coupled ◽  
The Brain

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

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