Systematic review of mechanistic evidence for TiO nanoparticle-induced lung carcinogenicity.

Nano-sized titanium dioxide particles (TiO NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO NPs in the lung are still unclear despite the vast number of and studies investigating TiO NPs. Here, we systematically reviewed the existing and mechanistic evidence of TiO NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens.

The Impact of Chronic Magnesium Deficiency on Excitable Tissues-Translational Aspects.

Neuromuscular excitability is a vital body function, and Mg is an essential regulatory cation for the function of excitable membranes. Loss of Mg homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg deficiency is an increasingly prevalent condition in the general population.

Neuron-astrocyte omnidirectional signaling in neurological health and disease.

Astrocytes are an abundantly distributed population of glial cells in the central nervous system (CNS) that perform myriad functions in the normal and injured/diseased brain. Astrocytes exhibit heterogeneous phenotypes in response to various insults, a process known as astrocyte reactivity. The accuracy and precision of brain signaling are primarily based on interactions involving neurons, astrocytes, oligodendrocytes, microglia, pericytes, and dendritic cells within the CNS.

Molecular Mechanisms Underlying Neuroinflammation Elicited by Occupational Injuries and Toxicants.

Occupational injuries and toxicant exposures lead to the development of neuroinflammation by activating distinct mechanistic signaling cascades that ultimately culminate in the disruption of neuronal function leading to neurological and neurodegenerative disorders. The entry of toxicants into the brain causes the subsequent activation of glial cells, a response known as 'reactive gliosis'. Reactive glial cells secrete a wide variety of signaling molecules in response to neuronal perturbations and thus play a crucial role in the progression and regulation of central nervous system (CNS) injury.

Glutathione in Brain Disorders and Aging.

Glutathione is a remarkably functional molecule with diverse features, which include being an antioxidant, a regulator of DNA synthesis and repair, a protector of thiol groups in proteins, a stabilizer of cell membranes, and a detoxifier of xenobiotics. Glutathione exists in two states-oxidized and reduced. Under normal physiological conditions of cellular homeostasis, glutathione remains primarily in its reduced form.

Wolframin-1-expressing neurons in the entorhinal cortex propagate tau to CA1 neurons and impair hippocampal memory in mice.

Abnormally phosphorylated tau, an early neuropathologic marker of Alzheimer’s disease (AD), first occurs in the brain’s entorhinal cortex layer II (ECII) and then spreads to the CA1 field of the hippocampus. Animal models of tau propagation aiming to recapitulate this phenomenon mostly show tau transfer from ECII stellate neurons to the dentate gyrus, but tau pathology in the dentate gyrus does not appear until advanced stages of AD. Wolframin-1–expressing (Wfs1) pyramidal neurons have been shown functionally to modulate hippocampal CA1 neurons in mice.

Alzheimer's disease brain-derived extracellular vesicles spread tau pathology in interneurons.

Extracellular vesicles are highly transmissible and play critical roles in the propagation of tau pathology, although the underlying mechanism remains elusive. Here, for the first time, we comprehensively characterized the physicochemical structure and pathogenic function of human brain-derived extracellular vesicles isolated from Alzheimer's disease, prodromal Alzheimer's disease, and non-demented control cases. Alzheimer's disease extracellular vesicles were significantly enriched in epitope-specific tau oligomers in comparison to prodromal Alzheimer's disease or control extracellular vesicles as determined by dot blot and atomic force microscopy.

Structural and functional features of medium spiny neurons in the BACHDΔN17 mouse model of Huntington's Disease.

In the BACHD mouse model of Huntington's disease (HD), deletion of the N17 domain of the Huntingtin gene (BACHDΔN17, Q97) has been reported to lead to nuclear accumulation of mHTT and exacerbation of motor deficits, neuroinflammation and striatal atrophy (Gu et al., 2015). Here we characterized the effect of N17 deletion on dorsolateral striatal medium spiny neurons (MSNs) in BACHDΔN17 (Q97) and BACWTΔN17 (Q31) mice by comparing them to MSNs in wildtype (WT) mice.

Treatment with Mesenchymal-Derived Extracellular Vesicles Reduces Injury-Related Pathology in Pyramidal Neurons of Monkey Perilesional Ventral Premotor Cortex.

Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices.

Functional roles of Kv1-mediated currents in genetically identified subtypes of pyramidal neurons in layer 5 of mouse somatosensory cortex.

We used voltage-clamp recordings from somatic outside-out macropatches to determine the amplitude and biophysical properties of putative Kv1-mediated currents in layer 5 pyramidal neurons (PNs) from mice expressing EGFP under the control of promoters for etv1 or glt. We then used whole cell current-clamp recordings and Kv1-specific peptide blockers to test the hypothesis that Kv1 channels differentially regulate action potential (AP) voltage threshold, repolarization rate, and width as well as rheobase and repetitive firing in these two PN types. We found that Kv1-mediated currents make up a similar percentage of whole cell K current in both cell types, and only minor biophysical differences were observed between PN types or between currents sensitive to different Kv1 blockers.

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex.

The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451-465, 2007), including among pyramidal cell subtypes.

Magnesium Effects on Nonsynaptic Epileptiform Activity in Leech Retzius Neurons.

The effects of Mg2+ on Ni(2+)-induced epileptiform bursting activity and input membrane resistance during this activity of leech Retzius neurons were examined using intracellular recordings. To induce epileptiform activity, 3 mmol/l NiCl2 was added into superfusing Ringer (Ri) saline. To test for dose-dependence of the effects of Mg2+ on the induced epileptiform activity, MgCl2 was added in concentrations from 1 mmol/l to 20 mmol/l Mg2+ to the Ni(2+)-containing Ri saline.

Ethanol and magnesium suppress nickel-induced bursting activity in leech Retzius nerve cells.

In the present study we have examined effects of ethanol and magnesium on Ni(2+)-induced bursting of leech Retzius cells. Saline with 3 mmol/l NiCl2 induced spontaneous bursting activity, characterized by rapid depolarizations to a plateau level during which bursts of action potentials occurred. To test for the mechanism of bursting initiation external Na+ was completely removed.