Journal of Anatomy最新文献

Schizophrenia (SCH) is a chronic and serious mental illness which puts an enormous burden on the individual, families, and society. It is well established that altered dopamine signaling and excitatory-inhibitory imbalance contributes to the symptoms of schizophrenia. Recent neuroimaging and histological studies suggest that the striatum is a key area involved in SCH, however, our knowledge of how specific cell neuronal subtypes of certain subcortical structures may be impaired is incomplete. To this date, no detailed investigation of the putamen has ever been published regarding neuroanatomical changes in SCH. Here we tested whether the density of calretinin immunopositive (CR+) neurons and DARPP32+ neurons is altered in the putamen of patients with SCH. We used immunohistochemistry to reveal CR+ and DARPP32+ neurons in six samples from patients with SCH and six age- and gender-matched control subjects. In line with previous studies, we detected small, medium, and large CR+ neurons. The density of small CR+ neurons was significantly lower in SCH (p = 0.0076). Medium and large CR+ and DARPP32+ neuronal density was not significantly different between groups. The present study substantiates previous results showing significantly lower density of small CR+ interneurons in the caudate nucleus in samples from patients with schizophrenia, highlighting the involvement of the striatum in the disorder. Our results warrant further studies focusing on the role of CR+ interneurons in the regulation of information processing in the fronto-striatal networks, evidently key structures in schizophrenia.

A general belief exists that tissue from anatomical donors, especially from the central nervous system (CNS), may not be suitable for histological investigation. This is based on the idea that fixation routinely used in embalming whilst optimal for enabling dissection, insufficiently preserves tissue architecture at the cellular level. However, anatomical donors represent a precious resource for microscopical investigation, provided that preservation is sufficient to enable recognition of structures at the histological level. This could considerably extend the biomedical knowledge currently gained from donations. In this study, we addressed this question and examined histologically, samples of medulla and spinal cord from donors from the Anatomical Gift Programme of RCSI in Dublin. Samples of medulla and spinal cord in the cervical, thoracic and lumbar regions were obtained with appropriate permissions from four different donors that had been previously embalmed for routine anatomical examination. The tissue obtained was processed for paraffin embedding and routine histology. Analysis revealed that several features were identifiable with good histological detail. A scoring system was applied to evaluate the level of histological preservation in the various samples by assessing the following parameters: tissue integrity, presence of leptomeninges along the entire section surface, distinction/adherence grey/white matter, identification of neurons, other cell nuclei, neuropil pattern, capillaries and other intraneural vessels. Lumbar spinal cord and to a lesser extent medulla and cervical spinal cord showed on average good quality of preservation. Conversely, thoracic spinal cord tended, in general, to be less well preserved. We can conclude that spinal cord and medulla samples from embalmed donors can be suitable for histological examination. These findings open new avenues of study of spinal cord and brain stem anatomy on cadaveric tissue from donors already existing in anatomy donation programmes. These results also pave the way for the potential development of new human models of study useful to spinal cord and brain stem researchers. Finally, this expands considerably the impact of the generosity of anatomical donors for the advancement of biomedical knowledge.

We discovered that the light entering a triangular ultramicrotome glass knife from the bottom exits the knife through its cutting edge, forming an oblique light sheet illumination suitable for imaging. We adopted this light sheet for side illumination of the sample blocks during sectioning on the ultramicrotome, for 3D imaging, and for targeting fluorescent features for confocal-, electron- and correlative microscopy. In this paper, we present a working prototype named CELS-3D (Cutting Edge Light Source, Three-Dimensional), a microscope mounted on an ultramicrotome. We characterised CELS-3D and applied it for 3D imaging of human liver spheroids with a diameter of approximately 500 μm. The structure of nuclei and tight junctions has been successfully reconstructed over the full spheroid volume. In contrast, a confocal microscope was unable to image spheroids to a depth of greater than 50 μm. CELS-3D shows fluorescence during serial sectioning in an online mode; therefore, it can apply for targeting fluorescence structures for correlative microscopy. We successfully applied CELS-3D for targeted correlative microscopy of human liver spheroids and C. elegans. The CELS-3D can be utilised for less- and non-transparent samples, which encompasses a range of applications, including operation biopsies, experimental organoids/spheroids, artificial cartilage, and bone, among others. The CELS-3D can be effortlessly mounted on the top of any commercially available ultramicrotome, and its operation is straightforward and intuitive.

Virtual microscopy is becoming increasingly common in both medical education and routine clinical practice. Virtual microscopy software is typically designed either for (1) training students in anatomy, histology, and histopathology, or (2) quantitative analysis-but not both simultaneously. QuPath is one of the most widely used software applications for histopathology image analysis in research and provides a comprehensive set of computational tools to evaluate histology slides. We have enhanced QuPath by developing a new extension, QuPath Edu, which adapts the software to function as an intuitive microanatomy learning environment. Additionally, we have created an entirely new, complementary software platform called OpenMicroanatomy, which provides an alternative way to access QuPath Edu teaching content through a web interface. These tools have been used in teaching of first year medical and dentistry students at the University of Oulu Medical Faculty, and we conducted a user survey for the Class of 2023 to assess the usability and student experience. In general, the introduced annotation and quiz features were appreciated by the students and the system usability of OpenMicroanatomy was considered excellent (SUS score 84.8). Together, these freely available tools enable teachers to develop and deploy innovative training material for anatomy, histopathology, quantitative analysis, and artificial intelligence in a wide range of contexts. This unique combination can provide the next generation of students with essential multidisciplinary skills.

Precise regulation of organ size and position is crucial for optimal organ function. Since the swim bladder is primarily responsible for buoyancy in teleosts, early development and subsequent inflation of the swim bladder should be appropriately controlled with the body growth. However, the underlying mechanism remains unclear. In this study, we show that the size and position of the swim bladder are physically constrained by the surrounding bones in zebrafish. Non-invasive micro-CT scanning revealed that the anterior edge of the swim bladder is largely attached to the os suspensorium, which is an ossicle extending medioventrally from the 4th centrum. Additionally, we observed that hoxc6a mutants, which lack the os suspensorium, exhibited an anterior projection of the swim bladder beyond the 4th vertebra. During the swim bladder development, we found that the counterclockwise rotation of the os suspensorium correlates with posterior regression of the swim bladder, suggesting that the os suspensorium pushes the swim bladder posteriorly into its proper position. Furthermore, our results revealed a close association between the posterior region of the swim bladder and the pleural ribs. In hoxaa cluster mutants with additional ribs, the swim bladder expanded posteriorly, accompanied by an enlarged body cavity. Taken together, our results demonstrate the importance of the surrounding bones in the robust regulation of swim bladder size and position in zebrafish.

The Weberian apparatus is a novel hearing adaptation that facilitates increased hearing sensitivity in otophysan fishes. The apparatus is a complex system composed of modifications to anterior vertebral elements, the inner ear, and the swim bladder. A critical piece of the system that often receives minor attention are the various ligaments that bridge these three regions. The most famous of the ligaments is the interossicular ligament, which connects the Weberian ossicle chain (scaphium–intercalarium–tripus). Several other ligaments are present, including the suspensor (tripus to parapophysis 4) and the triple ligament (tripus–os suspensorium–tunica externa). Here, by combining diffusible iodine-based contrast enhancement (DICE) and propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SRμCT) with classic histological methods, we shine new light on the first intercostal ligament (ICL1) and discuss its potential function in relation to the Weberian apparatus. ICL1 is nearly absent from the cypriniform literature, typically only mentioned in a general discussion together with other intercostal ligaments. This study examines the development and structure of ICL1 comparatively with the other definitive Weberian ligaments in the zebrafish (Danio rerio). We provide a comprehensive view of three-dimensional shape, development, and composition to generate hypotheses regarding potential functions of ICL1 within the greater Weberian apparatus. Given new detail presented herein regarding the structure of ICL1, modifications to rib 5 and parapophysis 4 for ICL1 attachment, and the alignment of ICL1 with the os suspensorium, we propose a supportive (anchoring) role of ICL1 to aid in minimizing non-optimal movement of the structures of the fourth vertebra. This addition would focus vibrations anteriorly through the ossicle chain with minimal signal loss in zebrafish and other species with similar Weberian apparatus morphologies. We conclude that ICL1 should be included in future analyses of Weberian apparatus function where ligaments are addressed.

Congenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin-dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13-related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13^tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X-gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT-qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high-resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13^tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13^tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13-related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.

A variety of anatomical techniques, imaging modalities, dyes and contrast agents, were used to document the mechanisms/routes whereby spinal cerebrospinal fluid (CSF) would move beyond the confines of the spinal dura in the American alligator, Alligator mississippiensis. Three pathways for CSF loss were identified: spinal arachnoid granulations, perineural flow along the spinal nerves, and lymphatic drainage (both along the surface of the dura and at the venous plexus surrounding the spinal ganglion). These same three pathways for spinal CSF loss have been documented in mammals, suggesting that they may be a common feature of (at least) amniotes. Crocodilians, including A. mississippiensis, have the largest epidural venous sinus system of any vertebrate, the present study suggests that, as in mammals, the venous complex of the alligator plays a direct role in regulating the absorption of CSF from the spinal compartment.

The sacroiliac joint (SIJ) exhibits significant variation in auricular surface morphology. This variation influences the mechanics of the SIJ, a central node for transmitting mechanical energy from upper body to lower limbs and vice versa. The impact of the auricular surface morphology on stress and deformation in the SIJ remains poorly understood to date. Computed tomography scans obtained from 281 individuals were included to extract the geometry of the pelvic ring. Then, the auricular surface area, SIJ cartilage thickness, and total SIJ cartilage volume were identified. Based on these reconstructions, 281 finite element models were created to simulate SIJ mechanical loading. It was found that SIJ cartilage thickness only weakly depended on age or laterality, while being strongly sex sensitive. Auricular surface area and SIJ cartilage volume depended weakly and non-linearly on age, peaking around menopause in females, but without significant laterality effect. Larger SIJs, characterized by greater auricular area and cartilage volume, exhibited reduced stress and deformation under loading. These findings highlight the significant role of SIJ morphology in its biomechanical response, suggesting a potential link between morphological variations and the risk of SIJ dysfunction. Understanding this relationship could improve diagnosis and targeted treatment strategies for SIJ-related conditions.