Neuronal Cells

Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in synaptic dysfunction during Alzheimer's disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by high levels of side-chain oxidized cholesterol known as 27-hydroxycholesterol (27-OH). Evidence from our laboratory has shown that elevated 27-OH can abolish synaptic connectivity during neuromaturation, but its effect on astrocyte function is currently unclear...

Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information...

Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis. The tumour necrosis factor receptor superfamily member 6 (TNFRSF6) gene encodes the Fas protein, and it participates in apoptosis induced in different cell types. This study aimed to explore TNFRSF6 function in SAE. The SAE mouse model was established by intraperitoneal injection of LPS in TNFRSF6-/- mice and C57BL/6J mice. Microglia were treated with LPS to establish the cell model. The learning, memory and cognitive functions in mice were tested by behavioral tests...

OBJECTIVES: Investigation of chronic homocysteine action on the excitability and N-methyl-D-aspartate (NMDA) sensitivity of the peripheral trigeminovascular system of rats. BACKGROUND: Migraine is a neurological disease that affects 15%-20% of the general population. Epidemiological observations show that an increase of the sulfur-containing amino acid homocysteine in plasma-called hyperhomocysteinemia-is associated with a high risk of migraine, especially migraine with aura...

BACKGROUND: Spinal cord injury (SCI) is an intractable neurological disease in which functions cannot be permanently restored due to nerve damage. Stem cell therapy is a promising strategy for neuroregeneration after SCI. However, experimental evidence of its therapeutic effect in SCI is lacking. This study aimed to investigate the efficacy of transplanted cells using stepwise combined cell therapy with human mesenchymal stem cells (hMSC) and induced pluripotent stem cell (iPSC)-derived motor neuron progenitor cells (iMNP) in a rat model of SCI...

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs...

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as a hallmark of POCD. However, safe and effective treatments of POCD are still lacking. Itaconate is an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we investigated the effects and underlying mechanism of 4-octyl itaconate (OI), a cell-permeable itaconate derivative, on POCD in aged mice...

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence...

Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both human and animal models. Although multiple studies have looked at transcriptional changes after social defeat stress, these studies primarily focus on bulk tissues, which might dilute important molecular signatures of social interaction in activated cells. In this study, we employed the Arc-GFP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) of resilient and susceptible animals...

Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos+ cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin...

The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice...

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1...

Gaucher disease (GD) is a lysosomal storage disorder caused by a mutation in the GBA1 gene, responsible for encoding the enzyme Glucocerebrosidase (GCase). Although neuronal death and neuroinflammation have been observed in the brains of individuals with neuronopathic Gaucher disease (nGD), the exact mechanism underlying neurodegeneration in nGD remains unclear. In this study, we used two induced pluripotent stem cells (iPSCs)-derived neuronal cell lines acquired from two type-3 GD patients (GD3-1 and GD3-2) to investigate the mechanisms underlying nGD by biochemical analyses...

While the double helical structure has long been its iconic representation, DNA is structurally dynamic and can adopt alternative secondary configurations. Specifically, guanine-rich DNA sequences can fold in guanine quadruplexes (G4) structures. These G4 play pivotal roles as regulators of gene expression and genomic stability, and influence protein homeostasis. Despite their significance, the association of G4 with neurodegenerative diseases such as Alzheimer's disease (AD) has been underappreciated. Recent findings have identified DNA sequences predicted to form G4 in sarkosyl-insoluble aggregates from AD brains, questioning the involvement of G4-structured DNA (G4 DNA) in the pathology...

Genetic variants in the apolipoprotein E ( APOE ) gene affect the onset and progression of Alzheimer's disease (AD). The APOE Christchurch ( APOE Ch) variant has been identified as the most prominent candidate for preventing the onset and progression of AD. In this study, we generated isogenic APOE3 Ch/ 3 Ch human induced pluripotent stem cells (iPSCs) from APOE3 / 3 healthy control female iPSCs and induced them into astrocytes. RNA expression analysis revealed the inherent resilience of APOE3 Ch/ 3 Ch astrocytes to induce a reactive state in response to inflammatory cytokines...

Laser microsurgery is a robust method to ablate specific cells in the nervous system and probe the functional consequences of their loss in the animal. By introducing focal lesions to small locations in the animal, laser microsurgery also enables disruptions of specific connections within neuronal circuits and the study of how the nervous system responds to precise forms of damage (for instance, damage to specific axons or dendrites, which have been found to evoke different kinds of responses in neurons). The MicroPoint laser is a pulsed dye laser that can be mounted onto any standard microscope, hence is an affordable alternative to two-photon lasers for providing high powered focal ablations...

Neurons extend their axons and dendrites over long distances and rely on evolutionarily conserved mechanisms to maintain the cellular structure and function of neurites at a distance from their cell body. Neurites that lose connection with their cell body following damage or stressors to their cytoskeleton undergo a programmed self-destruction process akin to apoptosis but using different cellular machinery, termed Wallerian degeneration. While first described for vertebrate axons by Augustus Waller in 1850, key discoveries of the enzymes that regulate Wallerian degeneration were made through forward genetic screens in Drosophila melanogaster Powerful techniques for genetic manipulation and visualization of single neurons combined with simple methods for introducing axotomy (neuron severing) to certain neuron types in Drosophila have enabled the discovery and study of the cellular machinery responsible for Wallerian degeneration, in addition to mechanisms that enable clearance of the resulting debris...

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis...

The extracellular matrix is recognized as an efficient and determining component in the growth, proliferation, and differentiation of cells due to its ability to perceive and respond to environmental signals. Applying three-dimensional scaffolds can create conditions similar to the extracellular matrix and provide an opportunity to investigate cell fate. In this study, we employed the PuraMatrix hydrogel scaffold as an advanced cell culture platform for the neural differentiation of stem cells derived from human breastmilk to design an opportune model for tissue engineering...

The lateral septum (LS) is involved in controlling anxiety, aggression, feeding, and other motivated behaviors. Lesion studies have also implicated the LS in various forms of caring behaviors. Recently, novel experimental tools have provided a more detailed insight into the function of the LS, including the specific role of distinct cell types and their neuronal connections in behavioral regulations, in which the LS participates. This article discusses the regulation of different types of maternal behavioral alterations using the distributions of established maternal hormones such as prolactin, estrogens, and the neuropeptide oxytocin...