Neuronal Growth Cones and Regeneration: Gridlock Within the Extracellular Matrix

The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatially regulated and is a dynamic living entity that is reshaped and redesigned on a continuous basis in response to changing needs. Some modifications are adaptive and some are maladaptive. It is the maladaptive responses that pose a significant threat to successful axonal regeneration and/or sprouting following traumatic and spinal cord injuries, and has been the focus of a myriad of research laboratories for many years. This review focuses largely on the extracellular matrix component, chondroitin sulfate proteoglycans, with certain comparisons to heparan sulfate proteoglycans, which tend to serve opposite functions in the central nervous system. Although about equally as well characterized as some of the other proteoglycans such as hyaluronan and dermatan sulfate proteoglycan, chondroitin sulfate proteoglycans are the most widely researched and discussed proteoglycans in the field of axonal injury and regeneration. Four laboratories discuss various aspects of chondroitin sulfate proteoglycans and proteoglycans in general with respect to their structure and function (Beller and Snow), the recent discovery of specific chondroitin sulfate proteoglycan receptors and what this may mean for increased advancements in the field (Shen), extracellular matrix degradation by matrix metalloproteinases, which sculpt and resculpt to provide support for outgrowth, synapse formation, and synapse stability (Phillips et al.), and the perilesion microenvironment with respect to immune system function in response to proteoglycans and central nervous system injuries (Jakeman et al.)

Proteoglycans: Road Signs for Neurite Outgrowth

Proteoglycans in the central nervous system play integral roles as traffic signals for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the injured central nervous system

Role of the Chondroitin Sulfate Proteoglycan, Neurocan, in Inhibition of Sensory Neurite Regeneration

In the adult mammalian brain and spinal cord, neuronal injury results in failed neurite regeneration, in part due to the up-regulation of chondroitin sulfate proteoglycans (CSPGs). CSPGs are molecules consisting of a protein core with covalently bound glycosaminoglycans (GAGS), specifically, chondroitin sulfate side-chains. The majority of CSPGs produced after injury originate from reactive astrocytes found in the glial scar surrounding the injury site. Although this milieu is very complex and involves more than just CSPGs, axonal regrowth may be improved if the expression of specific, highly inhibitory CSPGs produced after injury were attenuated selectively. Neurocan is one type of CSPG that is upregulated after injury and inhibits neurite regeneration. The over-arching goal of this study is to focus on the response and growth of sensory neurons in the presence of astrocytes that express neurocan, in relation to those astrocytes in which neurocan has been “knocked down” by shRNA transfection. In order to perform this analysis, the conditions needed for the co-culture experiment of chick astrocytes and chick neurons were optimized. A series of preliminary tests were performed on chick astrocytes, including a test to monitor the upregulation of CSPGs after treatment with Transforming Growth Factor-β (TGF-β), previously shown to mimic injury in an In vitro setting in rat astrocytes (G. Curinga et. al, 2008), and a test to demonstrate that chick astrocytes express Glial Fibrillary Acidic Protein (GFAP) in culture. Through these optimizations, co-culture analysis will be used to evaluate neuronal responses to neurocan. Other techniques used were tissue culture, immunofluorescence, and neurite outgrowth analyses

Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α(2)-adrenergic receptor (α(2)-AR) density in adolescent (35-days-old) rats, using [(3)H]RX821002 (5 nM). RESULTS: Sex-specific alterations of α(2)-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α(2)-AR in parietal cortex. CONCLUSION: These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine

REPORT OF THE SUNFLOWER WORKING GROUP

Cultivated sunflower (Helianthus annuus) is grown in many temperate, semi-dry regions of the world, often in rotation with small grain cereals such as wheat. The largest areas of sunflower cultivation in the US are in the northern plains (North and South Dakota) and southern, high plains (western Nebraska and Kansas, plus areas of Colorado and Texas) where the growing season is often too dry and/or too short for profitable soybean and corn production. Most commercial sunflower is the oilseed type; in addition, the crop is grown for confectionery seed and is common as an ornamental in home gardens throughout the US. The US is the center of diversity of the ancestral species of cultivated sunflower (Heiser 1954). The crop is capable of hybridizing with its wild progenitor, wild H. annuus, but most crosses with other Helianthus species such as H. petiolaris are unsuccessful or yield infertile F1 progeny (Rieseberg et al. 1999). Cultivated sunflower also occurs as a volunteer weed. Although volunteer domesticated plants can represent a significant portion of the weeds infesting subsequent crops (Auwarter and Nalewaja 1976; Gillespie and Miller 1984), they do not persist for more than one or two years under most cropping systems and are not known to spread. For these reasons, the working group focused on the consequences of gene flow to wild H. annuus. Wild H. annuus is an outcrossing annual that occurs in disturbed sites and is widespread throughout much of the US, reaching its greatest abundance in midwestern states (Heiser 1954). Wild sunflower occurs at elevations ranging from sea level to 3,000 meters and in a variety of habitats that include roadsides, agricultural fields, abandoned fields, construction sites, and rangeland. Populations are typically patchy and ephemeral, relying on the soil seed bank and long-distance dispersal for opportunities to become established in available clearings. This species occurs as a common but manageable weed of wheat, cultivated sunflower, corn, soybean, sugarbeet, sorghum, safflower, and other crops (Al-Khatib et al. 1998; Geir et al. 1996; Irons and Burnside 1982; Schweitzer and Bridge 1982; Teo-Sherrell 1996). Pollen from cultivated sunflower is certain to spread to adjacent wild populations by the movements of foraging insects, especially bees. Commercial sunflower seed companies are required to have 1.6-2.4 km of isolation between hybrid seed production fields and wild sunflower and/or other cultivated sunflower to prevent contamination by “foreign” pollen (e.g., Smith 1978; Schneiter 1997). The extent of pollen movement from the crop to wild sunflowers is greatest at the crop edge, where up to 42% of seeds can be crop-wild hybrids, diminishing to nearly zero at distances of 800-1,000 m (Arias and Rieseberg 1995; Whitton et al. 1997). F1 crop-wild hybrids are fertile and capable of backcrossing with nearby wild plants, but they typically produce fewer flower heads per plant than purely wild genotypes (Snow et al. 1998). Once crop genes enter wild populations, they can spread farther by both pollen and seed dispersal. Seeds can be transported inadvertently by farm equipment and as contaminants of hay, manure, topsoil, and seed lots. Whitton et al. (1997) and Linder et al. (1998) have documented long-term persistence of crop genes in populations of wild sunflower

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO