Inhibition of NADPH Oxidase Activation in Oligodendrocytes Reduces Cytotoxicity Following Trauma

Spinal cord injury is a debilitating neurological disorder that initiates a cascade of cellular events that result in a period of secondary damage that can last for months after the initial trauma. The ensuing outcome of these prolonged cellular perturbations is the induction of neuronal and glial cell death through excitotoxic mechanisms and subsequent free radical production. We have previously shown that astrocytes can directly induce oligodendrocyte death following trauma, but the mechanisms regulating this process within the oligodendrocyte remain unclear. Here we provide evidence demonstrating that astrocytes directly regulate oligodendrocyte death after trauma by inducing activation of NADPH oxidase within oligodendrocytes. Spinal cord injury resulted in a significant increase in oxidative damage which correlated with elevated expression of the gp91 phox subunit of the NADPH oxidase enzyme. Immunohistochemical analysis confirmed the presence of gp91 phox in oligodendrocytes in vitro and at 1 week following spinal cord injury. Exposure of oligodendrocytes to media from injured astrocytes resulted in an increase in oligodendrocyte NADPH oxidase activity. Inhibition of NADPH oxidase activation was sufficient to attenuate oligodendrocyte death in vitro and at 1 week following spinal cord injury, suggesting that excitotoxicity of oligodendrocytes after trauma is dependent on the intrinsic activation of the NADPH oxidase enzyme. Acute administration of the NADPH oxidase inhibitor apocynin and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate channel blocker 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione significantly improved locomotor behavior and preserved descending axon fibers following spinal cord injury. These studies lead to a better understanding of oligodendrocyte death after trauma and identify potential therapeutic targets in disorders involving demyelination and oligodendrocyte death.     

Macaque Monkeys Perceive the Flash Lag Illusion

Transmission of neural signals in the brain takes time due to the slow biological mechanisms that mediate it. During such delays, the position of moving objects can change substantially. The brain could use statistical regularities in the natural world to compensate neural delays and represent moving stimuli closer to real time. This possibility has been explored in the context of the flash lag illusion, where a briefly flashed stimulus in alignment with a moving one appears to lag behind the moving stimulus. Despite numerous psychophysical studies, the neural mechanisms underlying the flash lag illusion remain poorly understood, partly because it has never been studied electrophysiologically in behaving animals. Macaques are a prime model for such studies, but it is unknown if they perceive the illusion. By training monkeys to report their percepts unbiased by reward, we show that they indeed perceive the illusion qualitatively similar to humans. Importantly, the magnitude of the illusion is smaller in monkeys than in humans, but it increases linearly with the speed of the moving stimulus in both species. These results provide further evidence for the similarity of sensory information processing in macaques and humans and pave the way for detailed neurophysiological investigations of the flash lag illusion in behaving macaques.     

Fabrication of chitosan/poly(caprolactone) nanofibrous scaffold for bone and skin tissue engineering

Chitosan/poly(caprolactone) (CS/PCL) nanofibrous scaffold was prepared by a single step electrospinning technique. The presence of CS in CS/PCL scaffold aided a significant improvement in the hydrophilicity of the scaffold as confirmed by a decrease in contact angle, which thereby enhanced bioactivity and protein adsorption on the scaffold. The cyto-compatibility of the CS/PCL scaffold was examined using human osteoscarcoma cells (MG63) and found to be non toxic. Moreover, CS/PCL scaffold was found to support the attachment and proliferation of various cell lines such as mouse embryo fibroblasts (NIH3T3), murine aneuploid fibro sarcoma (L929), and MG63 cells. Cell attachment and proliferation was further confirmed by nuclear staining using 4',6-diamidino-2-phenylindole (DAPI). All these results indicate that CS/PCL nanofibrous scaffold would be an excellent system for bone and skin tissue engineering.     

Role of magnesium in alleviation of aluminium toxicity in plants

Magnesium is pivotal for activating a large number of enzymes; hence, magnesium plays an important role in numerous physiological and biochemical processes affecting plant growth and development. Magnesium can also ameliorate aluminium phytotoxicity, but literature reports on the dynamics of magnesium homeostasis upon exposure to aluminium are rare. Herein existing knowledge on the magnesium transport mechanisms and homeostasis maintenance in plant cells is critically reviewed. Even though overexpression of magnesium transporters can alleviate aluminium toxicity in plants, the mechanisms governing such alleviation remain obscure. Possible magnesium-dependent mechanisms include (i) better carbon partitioning from shoots to roots; (ii) increased synthesis and exudation of organic acid anions; (iii) enhanced acid phosphatase activity; (iv) maintenance of proton-ATPase activity and cytoplasmic pH regulation; (v) protection against an aluminium-induced cytosolic calcium increase; and (vi) protection against reactive oxygen species. Future research should concentrate on assessing aluminium toxicity and tolerance in plants with overexpressed or antisense magnesium transporters to increase understanding of the aluminium-magnesium interaction.     

Brain expression of the calcineurin inhibitor RCAN1 (Adapt78)

RCAN1 (Adapt78) is an endogenous inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. RCAN1 is expressed in multiple organs, especially heart, skeletal muscle and brain. In brain, it is thought to be important due to its strong expression, developmental regulation, abundance of target protein (calcineurin), and putative links to multiple brain-related disorders. Surprisingly, however, few studies have examined RCAN1 protein expression here. This has led to some confusion in the field over the exact nature and cell-type expression of isoform 4, the more studied of the two major RCAN1 protein isoforms, in brain. Here we characterize RCAN1 brain isoforms in more detail by assessing their size and distribution under conditions of calcium elevation, a hallmark of the isoform 4 response, and using rodent models to allow for more expanded analyses. We find that the 25-29 kDa version of this protein, reported in many non-brain studies, is indeed also present in neurons, and most observable after calcium induction. We also observe that expression of isoform 4 is not specific to neurons, as both microglia and astrocyte cells in culture exhibit a strong induction of isoform 4 protein following calcium stress that is not observable in non-stressed tissue sections. Isoform 1 expression is also observable in a primary glial cell-type (rat microglia). Finally, our observations confirm previous reports of low or non-detectable constitutive isoform expression in non-stressed glia, and of a larger sized, RCAN1 antibody-interacting species. These studies extend and complement previous studies on RCAN isoforms toward better understanding the role of RCAN1 in brain function and as a potential new target for treating calcineurin-related brain disorders.     

Prolactin Attenuates Neuroinflammation in LPS-Activated SIM-A9 Microglial Cells by Inhibiting NF-κB Pathways Via ERK1/2

Cellular and Molecular Neurobiology - Prolactin (PRL) is a pleiotropic hormone with multiple functions in several tissues and organs, including the brain. PRL decreases lesion-induced microgliosis...     

Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells

Molecular Biology Reports - The current study aimed to investigate the stimulatory effect of beta-adrenergic receptors (β-ARs) on brain derived neurotropic factor (BDNF) and cAMP response...     

Ion transport in broad bean leaf mesophyll under saline conditions

Main conclusion

Salt stress reduces the ability of mesophyll tissue to respond to light. Potassium outward rectifying channels are responsible for 84 % of Na ⁺ induced potassium efflux from mesophyll cells. Modulation in ion transport of broad bean (Vicia faba L.) mesophyll to light under increased apoplastic salinity stress was investigated using vibrating ion-selective microelectrodes (the MIFE technique). Increased apoplastic Na⁺ significantly affected mesophyll cells ability to respond to light by modulating ion transport across their membranes. Elevated apoplastic Na⁺ also induced a significant K⁺ efflux from mesophyll tissue. This efflux was mediated predominately by potassium outward rectifying channels (84 %) and the remainder of the efflux was through non-selective cation channels. NaCl treatment resulted in a reduction in photosystem II efficiency in a dose- and time-dependent manner. In particular, reductions in Fv′/Fm′ were linked to K⁺ homeostasis in the mesophyll tissue. Increased apoplastic Na⁺ concentrations induced vanadate-sensitive net H⁺ efflux, presumably mediated by the plasma membrane H⁺-ATPase. It is concluded that the observed pump’s activation is essential for the maintenance of membrane potential and ion homeostasis in the cytoplasm of mesophyll under salt stress.