Developmental regulation of zinc homeostasis in differentiating oligodendrocytes.

Oligodendrocytes develop through sequential stages and understanding pathways regulating their differentiation remains an important area of investigation. Zinc is required for the function of enzymes, proteins and transcription factors, including those important in myelination and mitosis. Our previous studies using the ratiometric zinc sensor chromis-1 demonstrated a reduction in intracellular free zinc concentrations in mature MBP+ oligodendrocytes compared with earlier stages (Bourassa et al.

Developmental regulation of zinc homeostasis in differentiating oligodendrocytes.

Oligodendrocytes develop through well characterized stages and understanding pathways regulating their differentiation remains an active area of investigation. Zinc is required for the function of many enzymes, proteins and transcription factors, including those important in myelination and mitosis. Our previous studies using the ratiometric zinc sensor chromis-1 demonstrated a reduction in intracellular free zinc concentrations in mature oligodendrocytes compared with earlier stages (Bourassa et al.

Bone Health Screening Practices Among Neurologists in Patients on Antiepileptic Drugs: A Quality Improvement Project.

Background: Pediatric patients with epilepsy are at risk for low vitamin D levels, increasing the risk for bone fractures, yet standardized bone health screening is not part of routine care.

Methods: We surveyed pediatric neurologists (n = 68) at our center regarding screening practices, using an 11-item survey; constructed a bone health treatment algorithm; and developed a training intervention to improve screening rates.

Results: The overall survey response rate was 47%.

Zinc homeostasis and zinc signaling in white matter development and injury.

Zinc is an essential dietary micronutrient that is abundant in the brain with diverse roles in development, injury, and neurological diseases. With new imaging tools and chelators selectively targeting zinc, the field of zinc biology is rapidly expanding. The importance of zinc homeostasis is now well recognized in neurodegeneration, but there is emerging data that zinc may be equally important in white matter disorders.

Chromis-1, a Ratiometric Fluorescent Probe Optimized for Two-Photon Microscopy Reveals Dynamic Changes in Labile Zn(II) in Differentiating Oligodendrocytes.

Despite the significant advantages of two-photon excitation microscopy (TPEM) over traditional confocal fluorescence microscopy in live-cell imaging applications, including reduced phototoxicity and photobleaching, increased depth penetration, and minimized autofluorescence, only a few metal ion-selective fluorescent probes have been designed and optimized specifically for this technique. Building upon a donor-acceptor fluorophore architecture, we developed a membrane-permeant, Zn(II)-selective fluorescent probe, chromis-1, that exhibits a balanced two-photon cross section between its free and Zn(II)-bound form and responds with a large spectral shift suitable for emission-ratiometric imaging. With a K of 1.

Effects of the neurotrophic factor artemin on sensory afferent development and sensitivity.

Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptor GFRalpha3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia (DRG and TG). These neurons co-express the heat, capsaicin and proton-sensitive channel TRPV1 and the cold and chemical-sensitive channel TRPA1.

Overexpression of artemin in the tongue increases expression of TRPV1 and TRPA1 in trigeminal afferents and causes oral sensitivity to capsaicin and mustard oil.

Artemin, a member of the glial cell line-derived neurotrophic factor (GDNF) family, supports a subpopulation of trigeminal sensory neurons through activation of the Ret/GFRalpha3 receptor tyrosine kinase complex. In a previous study we showed that artemin is increased in inflamed skin of wildtype mice and that transgenic overexpression of artemin in skin increases TRPV1 and TRPA1 expression in dorsal root ganglia neurons. In this study we examined how transgenic overexpression of artemin in tongue epithelium affects the anatomy, gene expression and calcium handling properties of trigeminal sensory afferents.

Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold.

Artemin, a neuronal survival factor in the glial cell line-derived neurotrophic factor family, binds the glycosylphosphatidylinositol-anchored protein GFRalpha3 and the receptor tyrosine kinase Ret. Expression of the GFRalpha3 receptor is primarily restricted to the peripheral nervous system and is found in a subpopulation of nociceptive sensory neurons of the dorsal root ganglia (DRGs) that coexpress the Ret and TrkA receptor tyrosine kinases and the thermosensitive channel TRPV1. To determine how artemin affects sensory neuron properties, transgenic mice that overexpress artemin in skin keratinocytes (ART-OE mice) were analyzed.

Effects of antenatal steroids on ischemic brain injury in near-term ovine fetuses.

Background: Hypoxia/ischemia in utero can result in brain damage to the fetus and newborn. Antenatal steroids are a routine part of the management of women who develop premature labor. Pretreatment of young postnatal rats with dexamethasone before hypoxic/ischemic insults has been reported to attenuate brain injury.

Effects of antenatal corticosteroids on regional brain and non-neural tissue water content in the ovine fetus.

Objective: We examined the effects of maternal corticosteroid administration on water content in regional tissue in ovine fetuses at 60%, 80%, and 90% of gestation.

Methods: After catheters were placed in the fetuses, the ewes were given four 6-mg doses of dexamethasone or placebo injections 12 hours apart over 48 hours. Water content of fetal tissue was determined 18 hours after the last injection was given to the ewes.