An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryos.

The effects of removing chondroitin sulfate from chondroitin sulfate proteoglycan molecules on guidance of retinal ganglion cell axons at the optic chiasm were investigated in a brain slice preparation of mouse embryos of embryonic day 13 to 15. Slices were grown for 5 hours and growth of dye-labeled axons was traced through the chiasm. After continuous enzymatic digestion of the chondroitin sulfate proteoglycans with chondroitinase ABC, which removes the glycosaminoglycan chains, navigation of retinal axons was disrupted. At embryonic day 13, before the uncrossed projection forms in normal development, many axons deviated from their normal course, crossing the midline at aberrant positions and invading the ventral diencephalon. In slices from embryonic day 14 embryos, axons that would normally form the uncrossed projection at this stage failed to turn into the ipsilateral optic tract. In embryonic day 15 slices, enzyme treatment caused a reduction of the uncrossed projection that develops at this stage. Growth cones in enzyme-treated slices showed a significant increase in the size both before and after they crossed the midline. This indicates that responses of retinal axons to guidance signals at the chiasm have changed after removal of the chondroitin sulfate epitope. We concluded that the chondroitin sulfate moieties of the proteoglycans are involved in patterning the early phase of axonal growth across the midline and at a later stage controlling the axon divergence at the chiasm

The proNGF-p75NTR-sortilin signalling complex as new target for the therapeutic treatment of Parkinson's disease.

Growing evidence has shown that the p75 neurotrophin receptor (p75NTR) may play important roles in controlling neuronal survival or cell apoptosis within the central nervous system in development, and in pathological or neural injury. Recent studies have further revealed that p75NTR acts as a "molecular signal switch" that determines cell death or survival by three processes. First, pro-nerve growth factor (proNGF) triggers cell apoptosis by its high affinity binding to p75NTR, while NGF induces neuronal survival with low-affinity binding. Second, p75NTR mediates cell death by combining with co-receptor sortilin, whereas it promotes neuronal survival through combination with proNGF. Third, release of the intracellular domain chopper or cleavaged "short p75NTR" can independently initiate neuronal apoptosis. We have identified the cell self-destructive proNGF-p75NTR-sortilin signalling apparatus assembled in ventral tier dopamine neurons of the substantia nigra pars compacta, suggesting that p75NTR signalling might be involved in selective cell death mechanisms of substantia nigra neurons or disease progression of Parkinson's disease (PD). In addition, experimental manipulation of p75NTR benefited cell survival of cholinergic or motor neurons and improved disease progression of the neurodegenerative diseases Alzheimer's disease and Amyotrophic lateral sclerosis. The proNGF-p75NTR-sortilin signalling complex may thus provide new target for neuroprotection of substantia nigra neurons and the therapeutic treatment of PD

Controlled Electrospray Generation of Non-Spherical Aqueous Microparticles

Symposium SM5—Aqueous Cytomimetic Materials - Symposium SM5.1: Hydrodynamics of Aqueous Two-Phase Systems (ATPS) Droplets - paper no. SM5.1.05Production of aqueous polymeric microparticles has attracted increasing interest because they benefit a variety of new biomedical applications such as cell encapsulation. Here we present a technique based on the application of electrospray to generate aqueous non-spherical microparticles using sodium alginate as emulsion phase and calcium chloride for continues phase. This approach allows the formation of calcium alginate microbeads with tunable sizes and shapes. We use a high voltage power supply to form the electric field, we apply a charge to the alginate solution that flows through a glass capillary with a tapered tip, and we ground a metallic ring that is positioned beneath the capillary tip. We investigate the effects of changing various parameters such as voltage, flow rate, capillary tip size, reagent concentration, and the distance from the capillary tip to the free interface of the calcium chloride bath, and discover parameter spaces that yield a variety of different shape and size particles. This technique of aqueous microparticles may have applications in drug delivery, enzyme immobilization, cell encapsulation and drug screening and further investigation of this technique can lead to a simple but high throughput method for generation of three-dimensional culture system in cancer studies

Pseudomonas aeruginosa adherence to human basement membrane collagen in vitro

The mechanisms for Pseudomonas aeruginosa colonisation in the airways of patients with bronchiectasis and cystic fibrosis are poorly understood. P. aeruginosa could evade mucociliary clearance by adhering to the basement membrane at areas denuded of,intact respiratory epithelium. The authors have developed an in vitro model to study P. aeruginosa adherence to human basement membrane type-IV collagen by using scanning electron microscopy. P. aeruginosa adherence density was determined as the number of P. aeruginosa per 20 microscope fields (2,000x) to log inocular size after incubation at 37°C for 45 min. The presence of phytohaemagglutinin (PHA)-E, which binds specifically to D-galactose-β1-4-D-N-acetylglucosamine, significantly reduced P. aeruginosa adherence density compared with control. The presence of heparin and calcium also significantly reduced P. aeruginosa adherence density. P. aeruginosa adherence was not affected by the presence of proline, trans-hydroxyproline, glycine, galactose, N-acetylneuraminic acid, N-acetylglucosamine or Arachis hypogea. Pseudomonas aeruginosa adherence probably acts via recognition of the D-galactose-β1-4-D-N-acetylglucosamine sequence on type-IV collagen and this process could be inhibited by heparin and calcium. As persistent Pseudomonas aeruginosa colonisation is detrimental to patients with cystic fibrosis and bronchiectasis and there is currently no effective treatment for its eradication, these results could lead to novel therapy for persistent Pseudomonas aeruginosa infection.link_to_OA_fulltex

Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.

Grafting of Schwann cell-seeded channels into hemisected adult rat thoracic spinal cords has been tested as a strategy to bridge the injured cord. Despite success in guiding axonal growth into the graft, regeneration across the distal graft-host interface into the host spinal cord was limited. We hypothesized that chondroitin sulfate (CS) glycoforms deposited at the gliotic front of the interface constitute a molecular barrier to axonal growth into the host cord. Because CS glycoforms deposited by purified astrocytes in vitro were removable by digestion with chondroitinase ABC, we attempted to achieve likewise by infusion of the enzyme to the host side of the interface. By 1 month post-treatment, significant numbers of regenerating axons crossed an interface that was subdued in macrophage/microglia reaction and decreased in CS-immunopositivity. The axons extended as far into the caudal cord as 5 mm, in contrast to nil in vehicle-infused controls. Fascicular organizations of axon-Schwann cell units within the regenerated tissue cable were better-preserved in enzyme-treated cords than in vehicle-infused controls. We conclude that CS glycoforms deposited during gliosis at the distal graft-host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord.link_to_subscribed_fulltex

Neural stem cells harvested from live brains by antibody-conjugated magnetic nanoparticles.

It stems from the magnetism: The extraction of stem/progenitor cells from the brain of live animals is possible using antibodies conjugated to magnetic nanoparticles (Ab-MNPs). The Ab-MNPs are introduced to a rat's brain with a superfine micro-syringe. The stem cells attach to the Ab-MNPs and are magnetically isolated and removed. They can develop into neurospheres and differentiate into different types of cells outside the subject body. The rat remains alive and healthy

Neural stem cells harvested from live brains by antibody-conjugated magnetic nanoparticles.

It stems from the magnetism: The extraction of stem/progenitor cells from the brain of live animals is possible using antibodies conjugated to magnetic nanoparticles (Ab-MNPs). The Ab-MNPs are introduced to a rat's brain with a superfine micro-syringe. The stem cells attach to the Ab-MNPs and are magnetically isolated and removed. They can develop into neurospheres and differentiate into different types of cells outside the subject body. The rat remains alive and healthy