Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that results in motor, sensory, cognitive, and affective deficits. Hippocampal demyelination, a common occurrence in MS, is linked to impaired cognitive function and mood. Despite this, the precise mechanisms underlying cognitive impairments in MS remain elusive.

Micro-RNA Signature in CSF Before and After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.

Background And Objectives: MicroRNAs (miRNAs) are regulators of gene expression and have been reported to be dysregulated in people with multiple sclerosis (pwMS). Autologous hematopoietic stem cell transplantation (aHSCT) is an immune-ablative treatment intervention for pwMS. Currently, it is unknown if aHSCT affects expression levels of miRNAs in CSF.

Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus.

Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear.

Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation.

Background: Mitochondrial DNA (mtDNA) is a pro-inflammatory damage-associated molecular pattern molecule and could be an early indicator for inflammation and disease activity in MS. Autologous hematopoietic stem cell transplantation (aHSCT) is a potent treatment for MS, but its impact on mtDNA levels in cerebrospinal fluid (CSF) remains unexplored.

Objectives: To verify elevated CSF mtDNA concentrations in MS patients and assess the impact of aHSCT on mtDNA concentrations.

Antibodies from serum and CSF of multiple sclerosis patients bind to oligodendroglial and neuronal cell-lines.

Multiple sclerosis is a highly complex and heterogeneous disease. At the onset it often presents as a clinically isolated syndrome. Thereafter relapses are followed by periods of remissions, but eventually, most patients develop secondary progressive multiple sclerosis.

Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab.

Importance: B-cell-depleting monoclonal antibodies are widely used for treatment of multiple sclerosis but are associated with an impaired response to vaccines.

Objective: To identify factors associated with a favorable vaccine response to tozinameran.

Design, Setting, And Participants: This prospective cohort study was conducted in a specialized multiple sclerosis clinic at a university hospital from January 21 to December 1, 2021.

Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons.

Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2.

Thalassemia Patients from Baluchistan in Pakistan Are Infected with Multiple Hepatitis B or C Virus Strains.

There are an estimated 2,000 children with β-thalassemia in the province Baluchistan of Pakistan. These children are at high risk of acquiring transfusion-transmitted infections (TTIs) due to their need of regular blood transfusions for survival. Therefore, we investigated the frequencies of TTIs among these multi-transfused patients in a region where the WHO guidelines for blood safety are not always followed.

Molecular forms of neurogranin in cerebrospinal fluid.

Neurogranin (Ng) is a 78 amino acid neuronal protein and a biomarker candidate for Alzheimer's disease (AD). Ng has been suggested to bind to calmodulin and phosphatidic acid via its centrally located IQ domain. Ng is cleaved within this functionally important domain, yielding the majority of fragments identified in cerebrospinal fluid (CSF), suggesting that cleavage of Ng may be a mechanism to regulate its function.

Author Correction: Accelerated neuronal and synaptic maturation by BrainPhys medium increases Aβ secretion and alters Aβ peptide ratios from iPSC-derived cortical neurons.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Accelerated neuronal and synaptic maturation by BrainPhys medium increases Aβ secretion and alters Aβ peptide ratios from iPSC-derived cortical neurons.

One of the neuropathological hallmarks of Alzheimer's disease (AD) is cerebral deposition of amyloid plaques composed of amyloid β (Aβ) peptides and the cerebrospinal fluid concentrations of those peptides are used as a biomarker for AD. Mature induced pluripotent stem cell (iPSC)-derived cortical neurons secrete Aβ peptides in ratios comparable to those secreted to cerebrospinal fluid in human, however the protocol to achieve mature neurons is time consuming. In this study, we investigated if differentiation of neuroprogenitor cells (NPCs) in BrainPhys medium, previously reported to enhance synaptic function of neurons in culture, would accelerate neuronal maturation and, thus increase Aβ secretion as compared to the conventional neural maintenance medium.

Expression and secretion of synaptic proteins during stem cell differentiation to cortical neurons.

Synaptic function and neurotransmitter release are regulated by specific proteins. Cortical neuronal differentiation of human induced pluripotent stem cells (hiPSC) provides an experimental model to obtain more information about synaptic development and physiology in vitro. In this study, expression and secretion of the synaptic proteins, neurogranin (NRGN), growth-associated protein-43 (GAP-43), synaptosomal-associated protein-25 (SNAP-25) and synaptotagmin-1 (SYT-1) were analyzed during cortical neuronal differentiation.

Alzheimer-associated cerebrospinal fluid fragments of neurogranin are generated by Calpain-1 and prolyl endopeptidase.

Background: Neurogranin (Ng) is a small 7.6 kDa postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), both as a full-length molecule and as fragments from its C-terminal half. Ng is involved in postsynaptic calcium (Ca) signal transduction and memory formation via binding to calmodulin in a Ca-dependent manner.

Role of NOX2-Derived Reactive Oxygen Species in NK Cell-Mediated Control of Murine Melanoma Metastasis.

The NADPH oxidase of myeloid cells, NOX2, generates reactive oxygen species (ROS) to eliminate pathogens and malignant cells. NOX2-derived ROS have also been proposed to dampen functions of natural killer (NK) cells and other antineoplastic lymphocytes in the microenvironment of established tumors. The mechanisms by which NOX2 and ROS influence the process of distant metastasis have only been partially explored.

Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation.

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development.