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Although previous studies have demonstrated that the hippocampus plays a role in pain processing, the role of hippocampal subfields is uncertain. The goal of this study was to examine the relationship between hippocampal subfield volumes and chronic pain in nondemented older adults. The study sample included 86 community-residing adults age 70 or older who were free of dementia and recruited from the Einstein Aging Study. Chronic pain was defined as pain over the last 3 months, that was moderate or severe (minimum rating of 4 out of 10) most, or all of the time. Hippocampal subfield volumes were estimated using FreeSurfer software. We modeled the association between chronic pain and hippocampal and subfield volume using linear regression. The sample had a mean age of 80 and was 58% female. Chronic pain, present in 55% of the sample, was associated with smaller right and total hippocampal volumes, particularly in women, after adjusting for age, education, and intracranial volume (eTICV). In addition, in women, volume was significantly reduced in participants with chronic pain in right CA2-3 (β=-0.35, p=0.010), right CA4-DG (β=-0.35, p=0.011), left presubiculum (β=-0.29, p=0.030), and left fimbria (β=-0.30, p=0.023). In men, chronic pain was not associated with the volume of any of the hippocampal subfield volumes. Chronic pain in women is associated with a reduction in the volume of right hippocampus and also selected hippocampal subfields. Future studies should clarify the mechanisms underlying the association between regional hippocampal volumes and chronic pain, particularly in women., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Neurofilaments (NFs) were radiolabeled in the optic systems of mice. The leading edge of the radiolabeled NF waveform was distinguished near the injection site (the eye) both by liquid scintillation spectroscopy and visually from fluorographs. The fastest NFs were found to be translocated at rates of between 72 and 144 mm/day. It appears that the continuous (maximal) operation of the slow axonal transport machinery can move polymers intra-axonally at rates one hundred times greater than those previously reported.

Neurofilament distributions were mathematically characterized in four chicken somatic motor axons at each of four histologically distinct regions: compact myelinated regions, compact myelinated regions associated with Schwann cell nuclei, Schmidt-Lanterman clefts, and nodes of Ranvier. Compact myelinated regions had the largest cross-sectional areas, the lowest neurofilament densities, and the most random neurofilament organizations--nodes of Ranvier had the smallest cross-sectional areas, the highest neurofilament densities, and the most ordered architectures. In these myelinated axons, the closest natural neurofilament spacing was 25 nm. Mathematical analyses of serial sections suggested that neurofilament interactions are sufficiently weak and transient to permit a full range of variation from random to ordered cytoskeletal architectures as the neurofilaments move longitudinally through the few micron span of the paranodal-nodal region of a single axon.

Ultrastructural morphometry was used to document the non-random spatial distributions of organelles within the compact myelinated region of avian oculomotor axons. These regions contain large numbers of loosely packed neurofilaments (NFs) (241/microns 2) and only a relatively small number of microtubules (MTs) (4/microns 2), mitochondria (0.6/microns 2), and smooth endoplasmic reticulum (SER) (1.6/microns 2). Random co-occurrences between the relatively sparsely distributed MTs, mitochondria, and SER are probably infrequent in these axons. The actual co-occurrences of MTs, mitochondria, and SER with MTs were counted and compared to the co-occurrences expected in a random Poisson distribution. At long distances (200 nm), the co-occurrences were random. At shorter distances (40 nm and less), MTs were still randomly associated with other MTs. However, at these shorter distances, the spatial associations of mitochondria with MTs and of SER with MTs were not random; such preferential stable associations may be produced by specific MT associated cross-bridging proteins. In axons, MTs tend to be clustered together, giving the appearance of MT bundles. We propose that the MT-MT bundling is an indirect result of MT concentration along the continuous intra-axonal SER network, to which the MTs are apparently tied directly by dynamic molecular cross-bridges.

The cross-sectional architecture of the axon and the area of its surrounding Schwann cell were quantified at selected histological regions along the length of avian myelinated axons. The number of neurofilaments (NFs), the density of NFs, axoplasmic area, and Schwann cell cross-sectional area were measured. These parameters were examined at Schmidt-Lanterman (S-L) clefts, at paranodal-nodal regions, and at regions of compact myelin Schwann cell nuclei. The results were then compared with the same parameters in adjacent compact myelinated regions of the same axons. At S-L clefts, paranodal-nodal regions, and Schwann cell nuclei, the axonal areas were smaller and the NF densities were higher than at compact myelinated regions. From other studies, it has been suggested that NF organization is responsive to local compressive forces--NF packing density tends to increase with increasing compression of the axon. We found that the NF packing densities were relatively small and the axon diameters were relatively large in the compact myelinated regions; this result suggests that in these axonal regions external constraints on axonal architecture are minimal. The higher NF packing densities and smaller axon diameters in the other histological regions suggest that external compressive effects on the axon increase in the following order: simple compact myelin less than Schwann cell nucleus less than S-L cleft less than paranodal-nodal region. Ultrastructural comparisons of these 4 histological regions show that the Schwann cell cross-sectional areas differ reproducibly, and this is consistent with the idea that variations in the organization of extra-axonal elements that envelop the axon produce different amounts of physical constraint on the axon and that this can affect the amount of external pressure on the internal architecture of the axon.

The window method of radiolabeled protein analysis was used to study the transport kinetics of axonally transported cytomatrix proteins as they move through segments of mouse optic axons. Three slow component b (SCb) proteins--actin, a 30 kDa protein, and clathrin--were radiolabeled in the eye and were followed for up to 119 days by quantitative one-dimensional gel electrophoresis. These proteins appeared first in the optic nerve, next in the tract, and last in the superior colliculus. All of the radiolabeled proteins had passed through the optic axons and had been effectively removed from the terminals by 119 days. Two different axonal segments ('windows') were examined in detail: a segment of the axon shaft region in the optic tract, and a segment of axon terminal region in the midbrain superior colliculus. The median transit times of the 3 proteins were 53-100% longer in the colliculus than in the tract, and the pulse transients (the total area under the transport curve in each window) were 180-350% larger in the colliculus than in the tract. These results indicate that at least certain cytomatrix and cytoskeletal proteins have longer residence times in the terminal regions than in the axon proper.

To distinguish the relative roles of the intrinsic and the extrinsic determinants of axonal branching shapes, a number of key branch parameters were measured under a variety of conditions. Branch shapes of frog and of chick axons were analyzed in tissue culture, and these in vitro patterns were compared with in vivo branch patterns of axons in tadpole tail fins. The shape of a branch junction can be characterized by the sizes of its branch angles. In all cases, branch junctions had only two branches (3 branch angles), and the bifurcation angle between them was usually the smallest. The shape of the branch junction was constant in a wide variety of environments, but the exact branch angles, as well as the numbers of branches per axon and the numbers of axons per neuron, could be modulated by changes in the substrate adhesivity.

Sparse, dissociated cultures of embryonic Xenopus CNS neurons were grown with and without NGF. Under both conditions the same number of neurons survived and extended neurites, and under both conditions the neurites moved at approximately the same overall rates and with the same degree of straightness. On the other hand, neurons in the NGF-supplemented cultures had more neurites and these neurites branched 64% more often. Detailed measurements showed that the axons elongated 44% faster in NGF and that this increase could be ascribed to a selective increase in the stepping rate of axonal elongation. These observations raise the possibility that NGF may selectively modulate the rate of movement of the core cytoskeleton of the axon.

The transport kinetics of 3 radiolabeled slow component b (SCb) proteins (a 30 kDa protein, clathrin, and actin) were examined in the axons of mouse retinal ganglion cells. To view the transit of these proteins through the entire optic pathway between the eye and the target cells, we used two different windows: (1) a 2 mm segment from the optic nerve located 3-5 mm from the eye, and (2) a 2 mm segment from the optic tract located past the chiasm 6-8 mm from the eye. The radiolabeled proteins from these windows were separated by 1- and 2-dimensional SDS-PAGE, and the individual radiolabeled bands were quantified. Radiolabeled proteins entered and cleared the optic axons between 1 and 119 days post-labeling. All these proteins had broader transport waves in the more distal optic tract window than in the more proximal optic nerve window. The spreading of transport waves as they advance along the axon appears to be produced by a playing out of the natural heterogeneity of axonal transport rates within each population of labeled proteins. Our results confirm the proposals that clathrin and the 30 kDa protein are transported principally with SCb and that actin is transported both with SCb and with SCa. Although these proteins can be generally classified with SCb, their detailed kinetics differed (for example, their median transit times differed) and, in summary, their characteristic rates of movement can be ordered as: clathrin greater than 30 kDa protein greater than actin.(ABSTRACT TRUNCATED AT 250 WORDS)