In this study, large areas of goldfish telencephalon were ablated including rostral nucleus preopticus periventriculare (rNPP), and degenerating axons were traced by a modified Fink and Heimer procedure. The lesioning procedure ablated large regions of area dorsalis telencephali pars medialis, centralis, and dorsolateral complex; and completely removed area ventralis telencephali pars dorsalis, ventralis, and lateralis. In addition, the supracommissural nucleus and rNPP were lesioned specifically because both nuclei have been thought to be involved in courtship behavior and endocrine control of reproduction. This investigation demonstrated extensive fiber projections from telencephalic nuclei and/or rNPP to the hypothalamus. Lesioned telencephalon and/or rNPP projected bilaterally to nucleus preopticus and the suprachiasmatic nucleus and unilaterally to the following tuberal nuclei: nucleus anterior tuberis, and the lateral hypothalamic nucleus. A much larger fiber projection to the inferior lobe nuclei was also observed with a large contralateral as well as ipsilateral input.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21019号 / 医博第4365号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 別所 和久, 教授 安達 泰治, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Light and electron microscopic degeneration studies were used to examine the telencephalotectal pathway in goldfish. Both techniques showed that each telencephalic lobe sent bilateral projections to several tectal laminae. Degenerating synaptic terminals and fibers were observed in the major retinal projection lamina as well as in other tectal laminae. The terminals contained round to oval synaptic vesicles, asymmetric synapses and contacted relatively small postsynaptic profiles.

Retinal terminal profiles in the goldfish optic tectum were identified electron microscopically after (1) labeling with horseradish peroxidase and (2) in the early stages of degeneration in short‐term eye enucleates. All labeled terminals shared certain common morphological characteristics which were identical to those of a population of terminals in normal tecta. Terminals of this type disappeared 30 days after enucleation of the contralateral eye. Retinal terminal presynaptic profiles were characterized by (1) round and oval synaptic vesicles; (2) mitochondria with irregular, randomly oriented cristae, large intracristal spaces, dilated membrane spaces, and primarily light matrices; (3) a wide range in profile area, 0.06–6.82 μm2; (4) large numbers of synaptic vesicles per profile area 168± 33 synaptic vesicles per μm2; (5) asymmetric synapses; and (6) multiple synaptic contacts (1.46 ± 0.73 per terminal profile). The postsynaptic elements included both dendritic and, less commonly, pleomorphic vesicle‐containing profiles. The majority of postsynaptic dendritic profiles were small (0.01–0.40 μm2). Serial synaptic contacts were occasionally seen. The combination of vesicular and mitochondrial morphology (1 and 2 above) was necessary and sufficient to establish the retinal origin of a terminal, but use of such criteria would underestimate the number of retinotectal terminals by omitting those which did not have a mitochondrion in the plane of section. The number of such terminals was calculated from independent measurements, and the total number of retinal terminal profiles per area of neuropil was estimated.

Purpose. The present work hypothesized that proteolytic dissolution of intervertebral discs could induce biomechanical change comparable to the change observed in natural disc degeneration. A method to do such could be utilized for in vitro research where intersample differences in geometry and chemical makeup render it difficult to compare and aggregate results into generalized conclusions. Methods. Forty-one bovine coccygeal intervertebral discs were isolated with individual functional spinal units. Samples were loaded in three modes: compression/tension, flexion/extension, and axial rotation. The anulus fibrosus of each disc was injected with 200µl trypsin or fetal bovine serum (control) and incubated for an allotted period: 30 minute, 60 minutes, or 180 minutes. Mechanical loading was repeated and the load-displacement responses before and after treatment were compared as were the differences between each time group. Results. Significant change was observed in the discs' total range (stiffness), low range (laxity), and hysteresis. Changes in load-displacement response were observed to be correlated with both treatment and time. Conclusions. Enzymatic degeneration of intervertebral discs shows promise as a means to further understanding of disc mechanics in varying levels of degeneration. In virtually all cases, the trypsinized discs exhibited the increased joint laxity and decreased stiffness that is associated with early stage, natural disc degeneration.

Purpose: Examine neuromechanical alterations due to isolated and/or combined knee pain and effusion in functional movements. Methods: A 4X3 randomised controlled laboratory study with repeated measures was used. Nineteen, healthy volunteers (age: 22.4 ± 2.4 years) underwent four different treatments (control, effusion, pain, and pain/effusion) with a week wash out period. Ten near-infrared cameras with 43 reflective markers, 12 surface EMG electrodes, and two ground-embedded force platforms were used to record neuromechanical changes during functional movements (walking and drop landing). To induce pain, 5% sodium chloride (1 ml) was injected into the infrapatellar fat pad. To induce effusion, 0.9% sodium chloride (50 ml) was injected into the knee joint capsule. To induce pain/effusion, both injections were employed. No injection was used for the control. Subjects performed walking and a single leg drop landing in three time intervals: precondition (prior to injection), condition (immediate post injection), and postcondition (30 min post injection). To quantify pain perception, the visual analogue scale was measured every two minutes. Results: Under pain/effusion treatment, subjects walked slowly with a shorter stride length. Joint moments of plantarflexion, knee extension, knee abduction, and hip abduction were reduced. Subjects also showed a decrease at 20% and 80% of stance phase, and an increase in 50% in vertical ground reaction force (VGRF). Under the same treatment, subjects landed with a less peak VGRF with increased time to peak VGRF, alterations of joint angles (ankle dorsiflexion, knee extension, and hip adduction), and moments (knee extension, knee abduction, and hip abduction). Conclusions: Joint pain and effusion cause neuromechanical alterations in the lower extremity during functional movements. These compensatory strategies may alter joint loading, potentially resulting in acceleration of the joint degenerative process. We also recommend use of crutches following injury to avoid modifications of movement strategies.

TAR DNA Binding Protein-43 (TDP-43) proteinopathy is a disease pathology that underlies a broad field of neurodegenerative disorders. Most prominently, TDP-43 aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). The implication of TDP-43 in ALS, in particular, has helped initiate a cascade of research to determine the properties of the previously obscure protein. From these studies, it is now known that TDP-43 is a DNA and RNA binding protein, important for the splicing and regulation of many transcripts. In the disease state, TDP-43 is modified in a way that fuels its accumulation into cytoplasmic aggregates called inclusions. This paper will delineate the current understanding of the mechanisms behind TDP-43 proteinopathy and the resultant clinical conditions. The body of evidence firmly supports a clinical spectrum of TDP-43 proteinopathy that ranges between pure motor neuron disease (MND) and pure frontotemporal dementia (FTD). It also appears that the root cause of neurodegeneration in these disorders comes about through a combination of a gain of toxic function and a loss of normal TDP-43. Continued research into the molecular processes leading to the capitulation of TDP-43 holds great promise for the development of new drug targets to help treat the spectrum of TDP-43 proteinopathy.

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