A synapse-specific refractory period for plasticity at individual dendritic spines.

How newly formed memories are preserved while brain plasticity is ongoing has been a source of debate. One idea is that synapses which experienced recent plasticity become resistant to further plasticity, a type of metaplasticity often referred to as saturation. Here, we probe the local dendritic mechanisms that limit plasticity at recently potentiated synapses.

Editorial on Special Issue "State-of-Art in mRNA Therapeutics and Gene Delivery".

RNA therapeutics are a class of medicines based on the insertion of a specific genetic message (mRNA) into the cells and the silencing or gene editing of a specific mRNA [...

Impact of Omega-3 on Endocannabinoid System Expression and Function, Enhancing Cognition and Behavior in Male Mice.

: Omega-3 long-chain polyunsaturated fatty acids (PUFAs) support brain cell membrane integrity and help mitigate synaptic plasticity deficits. The endocannabinoid system (ECS) is integral to synaptic plasticity and regulates various brain functions. While PUFAs influence the ECS, the effects of omega-3 on the ECS, cognition, and behavior in a healthy brain remain unclear.

Mesenchymal Stem Cells and Their Extracellular Vesicles: Therapeutic Mechanisms for Blood-Spinal Cord Barrier Repair Following Spinal Cord Injury.

Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB) exacerbating damage by allowing harmful substances and immune cells to infiltrate spinal neural tissues from the vasculature. This leads to inflammation, oxidative stress, and impaired axonal regeneration. The BSCB, essential for maintaining spinal cord homeostasis, is structurally similar to the blood-brain barrier.

Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity.

A series of novel carnosic acid derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid . The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2).

Lithium, Inflammation and Neuroinflammation with Emphasis on Bipolar Disorder-A Narrative Review.

This narrative review examines lithium's effects on immune function, inflammation and cell survival, particularly in bipolar disorder (BD) in in vitro studies, animal models and clinical studies. In vitro studies show that high lithium concentrations (5 mM, beyond the therapeutic window) reduce interleukin (IL)-1β production in monocytes and enhance T-lymphocyte resistance, suggesting a protective role against cell death. Lithium modulates oxidative stress in lipopolysaccharide (LPS)-activated macrophages by inhibiting nuclear factor (NF)-ƙB activity and reducing nitric oxide production.

5-HT Receptors in the BNST Modulate Contextual Fear Conditioning Without Affecting Acute Early Life Stress-Enhanced Fear Learning in Adult Rats.

Background/objectives: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with post-traumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with individuals exposed to early adverse experiences and women having increased vulnerability for diagnoses; however, the mechanisms of this increased vulnerability remain unknown.

High percentage of immune Th1 and Tc1 cells infiltrating visceral adipose tissue in people with obesity.

Subcutaneous (SAT) and visceral (VAT) adipose tissue dysfunction during the obesity onset can lead to increased expression of inflammatory molecules, and consequently to immune cell infiltration. The aim was to deeply characterize the T cells, those infiltrating SAT and VAT, compared to peripheral blood (PB), in individuals undergoing bariatric surgery. Forty-two adult individuals were recruited, SAT and VAT samples were collected.

Impact of Post-Traumatic Epilepsy on Mental Health and Multidimensional Outcome and Quality of Life: An NIDILRR TBIMS Study.

Traumatic brain injury (TBI) and subsequent post-traumatic epilepsy (PTE) often impair daily activities and mental health (MH), which contribute to long-term TBI-related disability. PTE also affects driving capacity, which impacts functional independence, community participation, and satisfaction with life (SWL). However, studies evaluating the collective impact of PTE on multidimensional outcomes are lacking.

HepG2 spheroids cultured in alginate microcapsules as a model for exploring mitochondrial and glycolytic metabolism using the Seahorse XFe24 Analyzer.

Mitochondria are affected by chemical substances and play a critical role in drug-induced liver injury (DILI). Chemical substances can have a significant impact on various cellular processes, such as the disruption of oxidative phosphorylation, oxidative stress, and alteration of glucose metabolism. Given the consequences of these effects, it is crucial to understand the molecular pathways of chemical substances in the context of hepatotoxicity to prevent and treat DILI.

Chaotic recurrent neural networks for brain modelling: A review.

Even in the absence of external stimuli, the brain is spontaneously active. Indeed, most cortical activity is internally generated by recurrence. Both theoretical and experimental studies suggest that chaotic dynamics characterize this spontaneous activity.

Building a growing genomic repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome.

Iron induces blood-brain barrier alteration contributing to cognitive impairment in β-thalassaemia mice.

Iron overload has been associated with cerebrovascular disease and cognitive impairment in β-thalassaemia patients, typically appearing earlier than in the general population. However, the mechanisms of iron overload on cerebrovascular pathology remain unclear. This study investigated the effects of heavy iron overload on the blood-brain barrier and neurohistology, particularly in the CA3 region of hippocampus and its contribution to cognitive impairment in β-thalassaemia mice.

Dynamic tracking of objects in the macaque dorsomedial frontal cortex.

A central tenet of cognitive neuroscience is that humans build an internal model of the external world and use mental simulation of the model to perform physical inferences. Decades of human experiments have shown that behaviors in many physical reasoning tasks are consistent with predictions from the mental simulation theory. However, evidence for the defining feature of mental simulation - that neural population dynamics reflect simulations of physical states in the environment - is limited.

Sodium channels in non-excitable cells: powerful actions and therapeutic targets beyond Hodgkin and Huxley.

Voltage-gated sodium channels (VGSCs) are best known for their role in the generation and propagation of action potentials in neurons, muscle cells, and cardiac myocytes, which have traditionally been labeled as 'excitable'. However, emerging evidence challenges this traditional perspective. It is now clear that VGSCs are also expressed in a broad spectrum of cells outside the neuromuscular realm, where they regulate diverse cellular functions.

Abnormal c-Fos expression in TetTag mice containing fos-EGFP.

Molecular and genetic techniques now allow selective tagging and manipulation of the population of neurons, often referred to as "engram cells," that were active during a specific experience. One common approach to labeling these cells is to use the transgenic mouse (TetTag). In addition to tagging cells active during learning, it is common to examine the reactivation of these cells using immediate early gene (IEG) expression as an index of neural activity.

Adolescent circadian rhythm disruption increases reward and risk-taking.

Introduction: Circadian rhythm disturbances have long been associated with the development of psychiatric disorders, including mood and substance use disorders. Adolescence is a particularly vulnerable time for the onset of psychiatric disorders and for circadian rhythm and sleep disruptions. Preclinical studies have found that circadian rhythm disruption (CRD) impacts the brain and behavior, but this research is largely focused on adult disruptions.

Comparison of different group-level templates in gradient-based multimodal connectivity analysis.

The study of large-scale brain connectivity is increasingly adopting unsupervised approaches that derive low-dimensional spatial representations from high-dimensional connectomes, referred to as gradient analysis. When translating this approach to study interindividual variations in connectivity, one technical issue pertains to the selection of an appropriate group-level template to which individual gradients are aligned. Here, we compared different group-level template construction strategies using functional and structural connectome data from neurotypical controls and individuals with autism spectrum disorder (ASD) to identify between-group differences.

Dual role of extracellular vesicles in neurodegenerative diseases.

Extracellular vesicles (EVs) are cell-to-cell interaction tools that are attracting increasing interest in the literature in two opposing areas. In addition to their role in physiological development, there is growing evidence of their involvement in healing and protective processes. However, EVs also mediate pathological conditions, particularly contributing to the progression of several chronic diseases, such as neurodegenerative diseases.

Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders.

Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder.

New low-dose curcumin derivative with therapeutic potential in Alzheimer's disease: Results from an in vitro and in vivo study in mice.

Curcumin has been proposed as a potential treatment for Alzheimer's disease (AD) due to its ability to inhibit amyloid-β (Aβ) peptide aggregates and to destabilise pre-formed ones. Derivative 27 was synthesized to improve low-dose efficacy in the context of AD. Its anti-inflammatory, antioxidant and anti-amyloidogenic activities were evaluated in chemico, in vitro using AD and neuroinflammation cell models, and in vivo using the double-transgenic APP/PS1 mice.