Exposure to tungsten particles via inhalation triggers early toxicity marker expression in the rat brain.

Objective: Our work is focused on tungsten, considered as an emerging contaminant. Its environmental dispersion is partly due to mining and military activities. Exposure scenario can also be occupational, in areas such as the hard metal industry and specific nuclear facilities.

Peripheral HMGB1 is linked to O pathology of disease-associated astrocytes and amyloid.

Introduction: Ozone (O) is an air pollutant associated with Alzheimer's disease (AD) risk. The lung-brain axis is implicated in O-associated glial and amyloid pathobiology; however, the role of disease-associated astrocytes (DAAs) in this process remains unknown.

Methods: The O-induced astrocyte phenotype was characterized in 5xFAD mice by spatial transcriptomics and proteomics.

The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment.

The mechanisms underlying how urban air pollution affects Alzheimer's disease (AD) are largely unknown. Ozone (O3) is a reactive gas component of air pollution linked to increased AD risk, but is confined to the respiratory tract after inhalation, implicating the peripheral immune response to air pollution in AD neuropathology. Here, we demonstrate that O3 exposure impaired the ability of microglia, the brain's parenchymal immune cells, to associate with and form a protective barrier around Aβ plaques, leading to augmented dystrophic neurites and increased Aβ plaque load.

The Use of Standardized Diesel Exhaust Particles in Alzheimer's Disease Research.

The mechanisms underlying how urban air pollution exposure conveys Alzheimer's disease risk and affects plaque pathology is largely unknown. Because particulate matter, the particle component of urban air pollution, varies across location, pollution source, and time, a single model representative of all ambient particulate matter is unfeasible for research investigating the role of ar pollution in central nervous system diseases. More specifically, the investigation of several models of particulate matter with enrichment of source-specific components are essential to employ, in order to more fully understand what characteristics of particulate matter affects Alzheimer's disease, including standardized diesel exhaust particles.

Xenobiotic transport and metabolism in the human brain.

Organisms have metabolic pathways responsible for eliminating endogenous and exogenous toxicants. Generally, we associate the liver par excellence as the organ in charge of detoxifying the body; however, this process occurs in all tissues, including the brain. Due to the presence of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), the Central Nervous System (CNS) is considered a partially isolated organ, but similar to other organs, the CNS possess xenobiotic transporters and metabolic pathways associated with the elimination of xenobiotic agents.

Circulating HMGB1 is elevated in veterans with Gulf War Illness and triggers the persistent pro-inflammatory microglia phenotype in male C57Bl/6J mice.

Gulf War Illness (GWI) is a chronic, multi-symptom peripheral and CNS condition with persistent microglial dysregulation, but the mechanisms driving the continuous neuroimmune pathology are poorly understood. The alarmin HMGB1 is an autocrine and paracrine pro-inflammatory signal, but the role of circulating HMGB1 in persistent neuroinflammation and GWI remains largely unknown. Using the LPS model of the persistent microglial pro-inflammatory response, male C57Bl/6J mice injected with LPS (5 mg/kg IP) exhibited persistent changes in microglia morphology and elevated pro-inflammatory markers in the hippocampus, cortex, and midbrain 7 days after LPS injection, while the peripheral immune response had resolved.

Diesel exhaust impairs TREM2 to dysregulate neuroinflammation.

Background: Air pollution has been linked to neurodegenerative diseases, including Alzheimer's disease (AD), and the underlying neuroimmune mechanisms remain poorly understood. TREM2 is a myeloid cell membrane receptor that is a key regulator of disease-associated microglia (DAM) cells, where loss-of-function TREM2 mutations are associated with an increased risk of AD. At present, the basic function of TREM2 in neuroinflammation is a point of controversy.

Schwann Cell Cultures: Biology, Technology and Therapeutics.

Schwann cell (SC) cultures from experimental animals and human donors can be prepared using nearly any type of nerve at any stage of maturation to render stage- and patient-specific populations. Methods to isolate, purify, expand in number, and differentiate SCs from adult, postnatal and embryonic sources are efficient and reproducible as these have resulted from accumulated refinements introduced over many decades of work. Albeit some exceptions, SCs can be passaged extensively while maintaining their normal proliferation and differentiation controls.

Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. Currently, there is no clear understanding of the mechanisms underlying the contribution of CAA to neurodegeneration. Despite the fact that CAA is highly associated with accumulation of Aβ, other types of amyloids have been shown to associate with the vasculature.

Deletion of mitochondrial calcium uniporter incompletely inhibits calcium uptake and induction of the permeability transition pore in brain mitochondria.

Ca influx into mitochondria is mediated by the mitochondrial calcium uniporter (MCU), whose identity was recently revealed as a 40-kDa protein that along with other proteins forms the mitochondrial Ca uptake machinery. The MCU is a Ca-conducting channel spanning the inner mitochondrial membrane. Here, deletion of the MCU completely inhibited Ca uptake in liver, heart, and skeletal muscle mitochondria.

Interconnections between the dorsal column nucleus and the cerebellum in a reptile.

Interconnections between the dorsal column nucleus and the cerebellum were examined in one group of reptiles, Caiman crocodilus. After anterograde tracer injections into the dorsal column nucleus, efferents terminated nearly exclusively in the white matter and ventral portion of the granule cell layer of the ipsilateral cerebellum. Subsequent to deposition of a retrograde tracer into the cerebellum, neurons in the central and ventral half of the dorsal column nucleus were labeled.