The interplay between glucose and ketone bodies in neural stem cell metabolism.

Glucose is the primary energy source for neural stem cells (NSCs), supporting their proliferation, differentiation, and quiescence. However, the high demand for glucose during brain development often exceeds its supply, leading to the utilization of alternative energy sources including ketone bodies. Ketone bodies, including ß-hydroxybutyrate, are short-chain fatty acids produced through hepatic ketogenesis and play a crucial role in providing energy and the biosynthetic components for NSCs when required. The interplay between glucose and ketone metabolism influences NSC behavior and fate decisions, and disruptions in these metabolic pathways have been linked to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Additionally, ketone bodies exert neuroprotective effects on NSCs and modulate cellular responses to oxidative stress, energy maintenance, deacetylation, and inflammation. As such, understanding the interdependence of glucose and ketone metabolism in NSCs is crucial to understanding their roles in NSC function and their implications for neurological conditions. This article reviews the mechanisms of glucose and ketone utilization in NSCs, their impact on NSC function, and the therapeutic potential of targeting these metabolic pathways in neurological disorders.

Animated teaching improves student learning of human gastrulation and neurulation.

Human embryology is a complex topic that brings together core components of anatomy and physiology to describe the developmental process from fertilisation to birth. Embryonic development is a challenging topic of study that is core to the curricula for health science students. There are challenges ingrained in teaching and learning embryology, due to the three-dimensional dynamic processes that occur as the embryo develops. This study aimed to develop and assess two newly developed animations depicting key processes in embryology, namely gastrulation and neurulation, as supplemental learning aids for students. Indeed, animated teaching tools to enhance the learning of gastrulation and neurulation are not widely available. A multi-disciplinary team of physiologists, biochemists, anatomists, and a computer scientist developed the animation sets. A student cohort of 81 first-year health science students were enrolled in this study over a period of three academic years. Both animations are in line with the course content of the first-year health science students undertaking the Human Health and Disease BSc at Trinity College Dublin, who were the study participants. Participants were randomly assigned to a non-animation control group and an animation group. Each set of animated teaching aids was broken down into individual clips which were given identifiable headings to allow the user to interchange between clips to facilitate a more personal learning experience. The animation group had open access to the animations for a three-week period. Questionnaires were designed to assess participants' attitude to the animations and their knowledge of embryology, both at the start of the study and three weeks later following access to the animations. Data presented herein indicate that students incorporated the animated teaching aids into digital home study and that the use of the animations acted as a supplemental tool that increased student knowledge in key areas of human embryology. From a qualitative point of view, students described the animations as enjoyable and helpful in visualising complex processes. This study indicates that the development of gastrulation and neurulation animated learning tools allow for a more engaging learning experience, facilitating student's engagement with academically challenging concepts in human embryology.

Dyad pedagogy in practical anatomy: A description of the implementation and student perceptions of an adaptive approach to cadaveric teaching.

Prior to the challenges imposed by the Covid-19 pandemic, anatomy practical sessions at Trinity College Dublin involved eight to 10 students per donor station, rotating between digital learning, anatomical models/osteology, and dissection activities for three hours weekly. To maintain cadaveric participation in the anatomy laboratory while adhering to distancing guidelines, a transition to dyad pedagogy was implemented. This mode of delivery allowed two students per donor station to spend one hour per week in the anatomy laboratory with all digital learning elements transferred to the virtual learning platform Blackboard as pre- and post-practical session learning activities. Dyad pedagogy has been explored in clinical settings and simulation procedural-based training but is yet to be fully verified in anatomy education. To determine the effectiveness of hybrid practical sessions and reduced donor to student ratios, the opinions of first year medical students were examined using an online questionnaire with a 51% response rate. Although students recognized the merits of more time in the anatomy laboratory, including opportunities for self-directed study and exposure to anatomical variation, they felt that having two students per station enabled sufficient hands-on time with the donor body and fostered learning opportunities that would not be possible with larger groups. Strong preferences for quality time with the donor body supported by online resources suggests this modality should be a key consideration in course design for anatomy curricula and emphasizes the importance of gauging students' preferences to optimize satisfaction and learning output when pivoting to blended learning strategies in anatomy education.

Reviving the anatomic past: Breathing new life into historic anatomical teaching tools.

The last two decades have seen a shift in the way anatomy education is delivered. With the introduction of blended learning, cadaveric dissection is no longer the be all and end all and, in many cases, the continuing role of anatomical teaching artefacts has declined after decades of prominence. While some institutions have abandoned their archaic anatomical collections and medical museums completely, others have invested in their technological enhancement. We describe the integration of historical teaching artefacts into contemporary anatomy education through the development of an interactive online e-platform and shed light on the enduring pedagogic value of past anatomical teaching specimen.

Radiology perspective on anatomy teaching in Australia and New Zealand.

INTRODUCTION: Anatomy pedagogy and radiologists involvement in teaching undergraduate anatomy varies widely. We surveyed radiologists practising in Australia and New Zealand to establish their opinions on their own experience of undergraduate anatomy and their view on the role of radiology in anatomy teaching. We also sought their views on the role of radiologists in anatomy teaching. METHODS: A short survey was designed on the Survey Monkey platform using the website surveymonkey.com. The survey was distributed to members of the Royal Australian and New Zealand College of Radiologists (RANCZR) as a link attached to a monthly e-newsletter with a short paragraph outlining its aim. RESULTS: Sixty-seven responses were eligible for analysis. 33% (22/67) were dissatisfied with their own anatomy training and 55% (38/67) felt that current graduates had an inadequate level of anatomy. 55% (38/67) indicated that radiology had not been a major part of their own undergraduate anatomy training. 58% (39/67) of respondents felt that non-radiology medical and para-medical professionals were not suitably qualified to teach radiologic anatomy. 75% (42/67) were of the opinion that radiology with 3-D support platforms may replace cadaveric dissection in the future, yet most were not familiar with 3-D platforms in current usage.

The Growth Response to Beta-Hydroxybutyrate in SH-SY5Y Neuroblastoma Cells is Suppressed by Glucose and Pyruvate Supplementation.

Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system and is commonly studied using the SH-SY5Y cell line. Its neoplastic and neurodevelopmental manifestations are characterised by a high glucose demand which maintains its high proliferative capacity. This metabolic phenotype may be utilised in dietary therapies such as the ketone diet which alter substrate availability and thus starve NB cells of their preferred biosynthetic requirements. However, the effects of ketone metabolism on cancer growth remain poorly understood due to the involvement of other metabolic substrates in experimental paradigms and complexities underlying the Warburg effect. We investigated how the primary ketone body beta-hydroxybutyrate (ßOHB) affects the growth of SH-SY5Y NB cells in the presence or absence of culture metabolic substrates. We demonstrated that while glucose deprivation reduced the growth and viability of SH-SY5Y cells, they proliferated and were initially unaffected by the addition of ßOHB. However, a growth response to ßOHB was subsequently revealed in media containing low levels of glucose, as well as in glucose and pyruvate deprived conditions. These data shed light on the roles of metabolic substrate availability as key determinants of the responses of SH-SY5Y NB cells to ketone supplementation.

Untangling the dorsal diencephalic conduction system: a review of structure and function of the stria medullaris, habenula and fasciculus retroflexus.

The often-overlooked dorsal diencephalic conduction system (DDCS) is a highly conserved pathway linking the basal forebrain and the monoaminergic brainstem. It consists of three key structures; the stria medullaris, the habenula and the fasciculus retroflexus. The first component of the DDCS, the stria medullaris, is a discrete bilateral tract composed of fibers from the basal forebrain that terminate in the triangular eminence of the stalk of the pineal gland, known as the habenula. The habenula acts as a relay hub where incoming signals from the stria medullaris are processed and subsequently relayed to the midbrain and hindbrain monoaminergic nuclei through the fasciculus retroflexus. As a result of its wide-ranging connections, the DDCS has recently been implicated in a wide range of behaviors related to reward processing, aversion and motivation. As such, an understanding of the structure and connections of the DDCS may help illuminate the pathophysiology of neuropsychiatric disorders such as depression, addiction and pain. This is the first review of all three components of the DDCS, the stria medullaris, the habenula and the fasciculus retroflexus, with particular focus on their anatomy, function and development.

Magnetic resonance diffusion weighted imaging using constrained spherical deconvolution-based tractography of the extracranial course of the facial nerve.

OBJECTIVE: To evaluate the accuracy of magnetic resonance diffusion weighted imaging (DWI) featuring constrained spherical deconvolution-based tractography in tracking the extracranial course of the facial nerve to provide a reliable facial nerve map to facilitate well-tolerated and effective tumor resection. STUDY DESIGN: Magnetic resonance DWI was conducted on 2 parotid-healthy cadaveric patients with various protocols to identify the best representation of the extracranial facial nerve tract. This was subsequently correlated to dissection of the facial nerves to ascertain anatomic validation. These protocols were applied to 2 live, parotid-healthy patients to assess feasibility of in vivo facial nerve tract identification. RESULTS: Correlations between imaged tracts and the anatomic course of the extracranial facial nerve were identified to an accuracy of 1 mm. The main trunk and bifurcation tracts were identified on imaging. Fractional anisometry values in cadaveric and live patients were within the range expected for the facial nerve within the parotid gland. CONCLUSIONS: Our results indicated the potential for accurate 3-dimensional visualization of the extracranial course of the facial nerve, which could have diagnostic implications in differentiating benign from malignant tumors and, crucially, neural involvement. Preoperative planning applications of DWI could help in planning surgical approaches and providing focused counseling.

Magnetic resonance spectroscopy across chronic pain disorders: a systematic review protocol synthesising anatomical and metabolite findings in chronic pain patients.

BACKGROUND: Chronic pain is pain greater than 3 months duration that may result from disease, trauma, surgery, or unknown origin. The overlap between the psychological, behavioural, and management aspects of pain suggest that limbic brain neurochemistry plays a role in chronic pain pathology. Proton magnetic resonance spectroscopy (1H-MRS) can evaluate in vivo brain metabolites including creatine, N-acetylaspartate, myo-inositol, choline, glutamate, glutamine, and gamma-aminobutyric acid in chronic pain; however, a comprehensive systemic review of metabolite expression patterns across all brain areas has yet to be performed. METHODS AND ANALYSIS: Online databases including PubMed/MEDLINE, Google Scholar, EMBASE, the Cochrane Library, OVID, and PsycINFO will be searched for articles relating to 1H-MRS and chronic pain. Study inclusion criteria will include ages of between 18 and 65 years with a definite diagnosis of chronic pain, no comorbidities, clearly stated brain volumes of interest, and imaging protocols, with comparisons to healthy controls. Two reviewers will extract data relating to volumes of interest, metabolites, study participant demographics, diagnostic method and pain scores, treatments and duration of treatment, scanner information, 1H-MRS acquisition protocols, and spectral processing software. Where possible, volumes of interest will be reassigned as regions of interest consistent with known regional anatomical and functional properties to increase the power and relevance of the analysis. Statistical analyses will then be conducted using STATA. A central common pathway may exist for chronic pain due to the behavioural manifestations and management similarities between its different types. The goal of this systemic review is to generate a comprehensive neurochemical theory of chronic pain in different brain compartments. SYSTEMATIC REVIEW REGISTRATION: This study is registered with PROSPERO CRD42018112640.

Diglossia in the Etiology of Schizophrenia: A Hypothesis.

A hypothesis offering diglossia as a potential risk factor for schizophrenia is presented. This is supported primarily by an account of the numerous co-occurrences between the diglossic phenomenon and the established risk factors and features of schizophrenia, such as language impairment, working memory dysfunction, social adversity, urbanicity, migration, and ethnicity, as well as some of the broader educational elements including illiteracy, reading deficits, and poor academic attainment. With an emphasis on the inherent role of language in schizophrenia and the demand for elucidating a mechanism behind its risk factors, we propose that a diglossic environment in childhood may constitute a neurodevelopmental insult predisposing to the development of the disorder. This relationship may be mediated by the reduced lateralization of language in the brain, which has been observed in relation to schizophrenia.

How much do preclinical medical students utilize the internet to study physiology?

Medical students increasingly utilize social media platforms to supplement their preclinical learning; however, the prevalence of social media use for physiology learning in medical education remains unclear. The aim of the present study was to determine how first-year medical students from both direct entry medicine and graduate entry medicine interacted with social media as a learning tool by assessing its prevalence, perceived benefits, favored platforms, and reason(s) for its use. Seventy-one percent of surveyed students (out of 139 participants) stated that they interacted with social media in general more than 12 times per week. However, 98% had previously used internet platforms to source physiology information, with 89.2% doing so at least once per week during term. YouTube was the primary source of learning for 76% of students. Significantly, 94% of students indicated that they would first search for answers online if they did not understand something in physiology rather than contacting their instructor in person or by e-mail. However, only 31% of students "fact-checked" physiology information obtained from online sources, by using textbooks, papers, and/or instructors. Our study has revealed that most preclinical medical students utilize social media extensively to study physiology. However, the absence of academic and ethical oversight, paired with students' lack of critical appraisal of possibly inaccurate information, does raise concerns about the overall utility of social media as part of physiology education.

Papez's Forgotten Tract: 80 Years of Unreconciled Findings Concerning the Thalamocingulate Tract.

The thalamocingulate tract is a key component of the Papez circuit that connects the anterior thalamic nucleus (ATN) to the cingulum bundle. While the other white matter connections, consisting of the fornix, cingulum bundle and mammillothalamic tract, were well defined in Papez's original 1937 paper, the anatomy of the thalamocingulate pathway was mentioned only in passing. Subsequent research has been unable to clarify the precise anatomical trajectory of this tract. In particular, the site of thalamocingulate tract interactions with the cingulum bundle have been inconsistently reported. This review aims to synthesize research on this least studied component of the Papez circuit. A systemic approach to reviewing historical anatomical dissection and neuronal tracing studies as well as contemporary diffusion magnetic resonance imaging studies of the thalamocingulate tract was undertaken across species. We found that although inconsistent, prior research broadly encompasses two differing descriptions of how the ATN interfaces with the cingulum after passing laterally through the anterior limb of the internal capsule. The first group of studies show that the pathway turns medially and rostrally and passes to the anterior cingulate region (Brodmann areas 24, 33, and 32) only. A second group suggests that the thalamocingulate tract interfaces with both the anterior and posterior cingulate (Brodmann areas 23 and 31) and retrosplenial region (Brodmann area 29). We discuss potential reasons for these discrepancies such as altering methodologies and species differences. We also discuss how these inconsistencies may be resolved in further research with refinements of terminology for the cingulate cortex and the thalamocingulate tract. Understanding the precise anatomical course of the last remaining unresolved final white matter tract in the Papez circuit may facilitate accurate investigation of the role of the complete Papez circuit in emotion and memory.

Radiologist's views on anatomical knowledge amongst junior doctors and the teaching of anatomy in medical curricula.

Reduced teaching resources, increasing student numbers and congested medical curricula have led to reports of inadequate anatomical knowledge among newly qualified doctors, placing scrutiny on pre-clinical education. We wished to gauge the opinions of practicing radiologists on undergraduate anatomy education. Members of the Irish Faculty of Radiologists were invited to complete a questionnaire based on anatomy teaching practices, its relevance and the standards of anatomical knowledge at graduation. Out of 67 respondents, 69% were of senior grade, with the majority working in diagnostic radiology. Respondents universally agreed that anatomy is central to radiology; however, decade of graduation significantly influenced radiologist's level of satisfaction with their anatomical knowledge at the start of their training. Fifty percent believed that the cadaver should remain the cornerstone of anatomy education. The vast majority of radiologists agreed that radiology and anatomy should be taught in tandem during pre-clinical training to better prepare students for clinical practice. Practicing radiologists believed they were best positioned to deliver radiology-based anatomy teaching. CT and MRI respectively were proposed as the preferred imaging modalities for teaching anatomy, although free comments showed varied opinion on how radiology and cadaveric anatomy should be integrated. Radiologists were also concerned with the anatomical knowledge of the junior doctor. This study may add to the debate concerning the vertical integration of anatomy in medical education and may help inform the delivery of radiology in the anatomy curriculum.

The distribution of the proteoglycan FORSE-1 in the developing mouse central nervous system.

Glycosylation is a major post-translational modification in which a carbohydrate known as a glycan is enzymatically attached to target proteins which regulate protein folding and stability. Glycans are strongly expressed in the developing nervous system where they play multiple roles during development. The importance of these glycan epitopes in neural development is highlighted by a group of conditions known as congenital disorders of glycosylation which lead to psychomotor difficulties, mental retardation, lissencephaly, microencephaly and epilepsy. One of these glycan epitopes, known as Lewis X, is recognised by the FORSE-1 antibody and is regionally expressed in the developing nervous system. In this study, we report the regional and temporal expression patterns of FORSE-1 immunolabelling during the periods of neurogenesis, gliogenesis and axonogenesis in developing mouse nervous system. We demonstrate the localisation of FORSE-1 on subsets of neuroepithelial cells and radial glial cells, and in compartments corresponding to axon tract formation. These spatial, temporal and regional expression patterns are suggestive of roles in the determination of different cell lineages and in the patterning of white matter during development, and help provide insights into the neuroanatomical regions affected by congenital disorders of glycosylation.

A comprehensive regional neurochemical theory in depression: a protocol for the systematic review and meta-analysis of 1H-MRS studies in major depressive disorder.

BACKGROUND: Magnetic resonance spectroscopy (MRS) is a non-invasive analytical technique that investigates the presence and concentrations of brain metabolites. In the context of major depressive disorder (MDD), MRS has revealed regional biochemical changes in GABA, glutamate, and choline across different brain compartments. Technical and methodological advances in MRS data acquisition, in particular proton-based 1H-MRS, have resulted in a significant increase in the incidence of reports utilizing the technique for psychiatric disorder research and diagnosis. The most recent comprehensive meta-analysis reviewing MRS in MDD stems from 2006. Using contemporary systemic reviews and meta-analysis, the aim is to first test a neurochemical circuit-based theory of depression and then to determine if clinical scores relate to metabolite concentrations before and during treatment. METHODS: Region-specific metabolite changes in MDD will be assessed by systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria will include participant age (18 to 65), English language studies, known regions of interest, and detailed documentation of 1H-MRS procedures. Reported brain regions will be standardized according neuroanatomical expertise allowing increased power of the meta-analysis. Regions of interest will initially include the hippocampus, thalamus, prefrontal cortex, anterior and posterior cingulate gyri, parietal lobe, and basal ganglia. Exclusion criteria will include comorbid psychiatric illness and drug use. Two independent reviewers will undertake all data extraction, while a third reviewer will check for reviewer discrepancies. Statistical analysis will be performed using STATA supplemented by Metan software and SPSS. DISCUSSION: This data will shed new light on the biochemical basis of depression in different brain regions, thereby highlighting the potential of MRS in identifying biomarkers and generating models of MDD and treatment response. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018091494.

Awakening Neuropsychiatric Research Into the Stria Medullaris: Development of a Diffusion-Weighted Imaging Tractography Protocol of This Key Limbic Structure.

The Stria medullaris (SM) Thalami is a discrete white matter tract that directly connects frontolimbic areas to the habenula, allowing the forebrain to influence midbrain monoaminergic output. Habenular dysfunction has been shown in various neuropsychiatric conditions. However, there exists a paucity of research into the habenula's principal afferent tract, the SM. Diffusion-weighted tractography may provide insights into the properties of the SM in vivo, opening up investigation of this tract in conditions of monoamine dysregulation such as depression, schizophrenia, addiction and pain. We present a reliable method for reconstructing the SM using diffusion-weighted imaging, and examine the effects of age and gender on tract diffusion metrics. We also investigate reproducibility of the method through inter-rater comparisons. In consultation with neuroanatomists, a Boolean logic gate protocol was developed for use in ExploreDTI to extract the SM from constrained spherical deconvolution based whole brain tractography. Particular emphasis was placed on the reproducibility of the tract, attention to crossing white matter tract proximity and anatomical consistency of anterior and posterior boundaries. The anterior commissure, pineal gland and mid point of the thalamus were defined as anatomical fixed points used for reconstruction. Fifty subjects were scanned using High Angular Resolution Diffusion Imaging (HARDI; 61 directions, b-value 1500 mm3). Following constrained spherical deconvolution whole brain tractography, two independent raters isolated the SM. Each output was checked, examined and cleaned for extraneous streamlines inconsistent with known anatomy of the tract by the rater and a neuroanatomist. A second neuroanatomist assessed tracts for face validity. The SM was reconstructed with excellent inter-rater reliability for dimensions and diffusion metrics. Gender had no effect on the dimensions or diffusion metrics, however radial diffusivity (RD) showed a positive correlation with age. Reliable identification and quantification of diffusion metrics of the SM invites further exploration of this key habenula linked structure in neuropsychiatric disorders such as depression, anxiety, chronic pain and addiction. The accurate anatomical localization of the SM may also aid preoperative stereotactic localization of the tract for deep brain stimulation (DBS) treatment.

The ketogenic diet in disease and development.

The ketogenic diet, low in carbohydrates and high in fat, was initially designed to reduce seizure onset in epilepsy. More recent evidence has shown its effectiveness in the treatment of movement and psychological disorders, and in general health maintenance. The cellular significance of ketone body metabolism during development and in the adult central nervous system is being revealed; however, the effects of replacing glucose with ketone bodies as the brain's primary energy source especially in pregnancy are not fully understood. In this mini-review, we highlight key findings related to the functional consequences of ketone body metabolism and monocarboxylic transporter expression throughout development and adulthood. We outline the therapeutic relevance of ketone bodies, and place a spotlight on the known effects of a maternal ketogenic diet on the developing brain.

Googling in anatomy education: Can google trends inform educators of national online search patterns of anatomical syllabi?

The role of e-learning platforms in anatomy education continues to expand as self-directed learning is promoted in higher education. Although a wide range of e-learning resources are available, determining student use of non-academic internet resources requires novel approaches. One such approach that may be useful is the Google Trends© web application. To determine the feasibility of Google Trends to gain insights into anatomy-related online searches, Google Trends data from the United States from January 2010 to December 2015 were analyzed. Data collected were based on the recurrence of keywords related to head and neck anatomy generated from the American Association of Clinical Anatomists and the Anatomical Society suggested anatomy syllabi. Relative search volume (RSV) data were analyzed for seasonal periodicity and their overall temporal trends. Following exclusions due to insufficient search volume data, 29 out of 36 search terms were analyzed. Significant seasonal patterns occurred in 23 search terms. Thirty-nine seasonal peaks were identified, mainly in October and April, coinciding with teaching periods in anatomy curricula. A positive correlation of RSV with time over the 6-year study period occurred in 25 out of 29 search terms. These data demonstrate how Google Trends may offer insights into the nature and timing of online search patterns of anatomical syllabi and may potentially inform the development and timing of targeted online supports to ensure that students of anatomy have the opportunity to engage with online content that is both accurate and fit for purpose. Anat Sci Educ 10: 152-159. © 2016 American Association of Anatomists.