scholarly journals Structural and Functional Aspects of the Neurodevelopmental Gene NR2F1: From Animal Models to Human Pathology

2021 ◽  
Vol 14 ◽  
Author(s):  
Chiara Tocco ◽  
Michele Bertacchi ◽  
Michèle Studer
Keyword(s):  
Thyroid Hormone Receptor ◽  
Clinical Signs ◽  
Autistic Traits ◽  
Network Activity ◽  
Mammalian Brain ◽  
Future Research ◽  
Cellular Models ◽  
Human Pathology ◽  
Developing Mouse Brain ◽  
Experimental Findings

The assembly and maturation of the mammalian brain result from an intricate cascade of highly coordinated developmental events, such as cell proliferation, migration, and differentiation. Any impairment of this delicate multi-factorial process can lead to complex neurodevelopmental diseases, sharing common pathogenic mechanisms and molecular pathways resulting in multiple clinical signs. A recently described monogenic neurodevelopmental syndrome named Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is caused by NR2F1 haploinsufficiency. The NR2F1 gene, coding for a transcriptional regulator belonging to the steroid/thyroid hormone receptor superfamily, is known to play key roles in several brain developmental processes, from proliferation and differentiation of neural progenitors to migration and identity acquisition of neocortical neurons. In a clinical context, the disruption of these cellular processes could underlie the pathogenesis of several symptoms affecting BBSOAS patients, such as intellectual disability, visual impairment, epilepsy, and autistic traits. In this review, we will introduce NR2F1 protein structure, molecular functioning, and expression profile in the developing mouse brain. Then, we will focus on Nr2f1 several functions during cortical development, from neocortical area and cell-type specification to maturation of network activity, hippocampal development governing learning behaviors, assembly of the visual system, and finally establishment of cortico-spinal descending tracts regulating motor execution. Whenever possible, we will link experimental findings in animal or cellular models to corresponding features of the human pathology. Finally, we will highlight some of the unresolved questions on the diverse functions played by Nr2f1 during brain development, in order to propose future research directions. All in all, we believe that understanding BBSOAS mechanisms will contribute to further unveiling pathophysiological mechanisms shared by several neurodevelopmental disorders and eventually lead to effective treatments.

scholarly journals A systematic PRISMA review of individuals with autism spectrum disorder in secure psychiatric care: prevalence, treatment, risk assessment and other clinical considerations

2018 ◽  
Vol 8 (1) ◽  
pp. 58-79 ◽  
Author(s):  
Clare S. Allely
Keyword(s):  
Autism Spectrum Disorder ◽  
Psychiatric Care ◽  
Psychiatric Hospitals ◽  
Autistic Traits ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Bibliographic Databases ◽  
Future Research ◽  
Content Type ◽  
Secure Psychiatric Care

Purpose Patients with autism spectrum disorder (ASD) present with specific assessment, specific difficulties, needs and therapeutic issues and therefore are a challenging group for forensic services. Given the challenge that individuals with ASD present to forensic services, the suggested increase in the number of this group within this setting and the relatively little amount of research which suggests they face a number of difficulties within the prison environment, the purpose of this paper is to identify and review all the studies which have been carried out investigating any aspect of ASD in relation to secure hospital settings. Design/methodology/approach Seven internet-based bibliographic databases were used for the present review. The review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Findings A total of 12 studies were included in this review; 3 looked at the prevalence of ASD in secure psychiatric hospitals. One study evaluated the clinical utility of the AQ screening tool to assess self-reported autistic traits in secure psychiatric settings. Three explored any type of characteristics of patients with ASD detained in secure psychiatric hospitals. One study investigated the experiences or quality of life of patients with an ASD detained in secure psychiatric care. Two studies investigated awareness, knowledge and/or views regarding patients with ASD held by staff working within secure psychiatric hospitals. Lastly, three studies (one of which was also included in the prevalence category above) looked at the effectiveness of interventions or treatment of patients with ASD in secure psychiatric hospitals. Clinical recommendations and future research directions are discussed. Originality/value To the author’s knowledge, this is the first review to explore what research has been carried out looking specifically at patients with ASD in relation to secure forensic settings.

Mumps as a Cause of Hydrocephalus

PEDIATRICS ◽  
1972 ◽  
Vol 50 (2) ◽  
pp. 346-347
Author(s):  
J. Hower ◽  
H. E. Clar ◽  
M. Düchting
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Intracranial Pressure ◽  
Head Circumference ◽  
Aqueductal Stenosis ◽  
Sudden Increase ◽  
Increased Intracranial Pressure ◽  
Cerebrospinal Fluid Flow ◽  
Human Pathology ◽  
Experimental Findings

We read Dr. Bray's communication with great interest. With actually three cases of aqueductal stenosis after mumps being recorded we cannot doubt that the experimental findings of Johnson and Johnson have a bearing on human pathology. Our patient, a 6½-year-old boy, underwent evaluation of his megacephalus five months before the onset of mumps. At that time a pneumoencephalogram could be obtained by lumbar filling. Cerebrospinal fluid flow was considered marginally adequate. Three months after mumps meningoencephalitis the patient presented with symptoms of increased intracranial pressure (papilledema, sudden increase in head circumference, and widening of the coronar suture).

scholarly journals Models of multiple system atrophy

2019 ◽  
Vol 51 (11) ◽  
pp. 1-10 ◽  
Author(s):  
He-Jin Lee ◽  
Diadem Ricarte ◽  
Darlene Ortiz ◽  
Seung-Jae Lee
Keyword(s):  
Animal Models ◽  
Multiple System Atrophy ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Lewy Bodies ◽  
Model Systems ◽  
Future Research ◽  
Cytoplasmic Inclusions ◽  
Cellular Models ◽  
Brain Extracts

AbstractMultiple system atrophy (MSA) is a neurodegenerative disease with diverse clinical manifestations, including parkinsonism, cerebellar syndrome, and autonomic failure. Pathologically, MSA is characterized by glial cytoplasmic inclusions in oligodendrocytes, which contain fibrillary forms of α-synuclein. MSA is categorized as one of the α-synucleinopathy, and α-synuclein aggregation is thought to be the culprit of the disease pathogenesis. Studies on MSA pathogenesis are scarce relative to studies on the pathogenesis of other synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies. However, recent developments in cellular and animal models of MSA, especially α-synuclein transgenic models, have driven advancements in research on this disease. Here, we review the currently available models of MSA, which include toxicant-induced animal models, α-synuclein-overexpressing cellular models, and mouse models that express α-synuclein specifically in oligodendrocytes through cell type-specific promoters. We will also discuss the results of studies in recently developed transmission mouse models, into which MSA brain extracts were intracerebrally injected. By reviewing the findings obtained from these model systems, we will discuss what we have learned about the disease and describe the strengths and limitations of the models, thereby ultimately providing direction for the design of better models and future research.

A Multi-User Computer-Aided Design Competition: Experimental Findings and Analysis of Team-Member Dynamics

2017 ◽  
Vol 17 (3) ◽  
Author(s):  
Brett Stone ◽  
John Salmon ◽  
Keenan Eves ◽  
Matthew Killian ◽  
Landon Wright ◽  
...  
Keyword(s):  
Computer Aided Design ◽  
Value Added ◽  
Future Research ◽  
Calendar Time ◽  
Competition Analysis ◽  
Computer Aided ◽  
Design Competition ◽  
Purdue Spatial Visualization Test ◽  
Experimental Findings ◽  
Aided Design

A competition for teams of three students using a prototype multi-user computer-aided design (MUCAD) tool was held to investigate various hypotheses regarding the performance of teams in such a setting. By comparing models from the competition to the same model in a single-user CAD environment, it is seen that use of a MUCAD system can significantly increase the value-added per unit of calendar time for a modeling effort. An investigation was also made into the causes of the performance differences among the various MUCAD teams which participated in the competition. Analysis of the results shows that teams that encouraged effective forms of communication and teams whose members scored similarly on the Purdue Spatial Visualization Test: Visualization of Rotations (PSVT:R) performed better than other teams. Areas of future research in analyzing teams in MUCAD environments are suggested.

scholarly journals Progress in Behavioral Game Theory

1997 ◽  
Vol 11 (4) ◽  
pp. 167-188 ◽  
Author(s):  
Colin F Camerer
Keyword(s):  
Game Theory ◽  
Social Values ◽  
Future Research ◽  
Backward Induction ◽  
Behavioral Game Theory ◽  
Dominated Strategies ◽  
Behavioral Game ◽  
Experimental Findings

Behavioral game theory aims to predict how people actually behave by incorporating psychological elements and learning into game theory. With this goal in mind, experimental findings can be organized into three categories: players have systematic 'reciprocated social values,' like desires for fairness and revenge. Phenomena discovered in studies of individual judgments and choices, like 'framing' and overconfidence, are also evident in games. Strategic principles, like irrelevance of strategy labels and timing of moves, iterated elimination of dominated strategies, and backward induction, are violated. Future research should incorporate these findings, along with learning and 'pregame theory,' into formal game theory.

scholarly journals Plants that cause photosensitivity in ruminants in Brazil

2016 ◽  
Vol 37 (4) ◽  
pp. 2009 ◽  
Author(s):  
Sheila Nogueira Ribeiro Knupp ◽  
Leonardo Sidney Knupp ◽  
Franklin Riet-Correa ◽  
Ricardo Barbosa Lucena
Keyword(s):  
Pyrrolizidine Alkaloids ◽  
Clinical Signs ◽  
Mechanisms Of Action ◽  
Diagnostic Methods ◽  
Future Research ◽  
Steroidal Saponins ◽  
Poisonous Plants ◽  
Toxic Compounds ◽  
Toxic Compound ◽  
Ammi Majus

This study aimed to review the mechanisms of action, clinical signs, pathology, and toxic compounds of plants that cause photosensitivity in ruminants. In addition, we sought to clarify the diagnostic methods and prophylaxis of photosensitivity-induced plants. Photosensitizing plants constitute an important group of poisonous plants in Brazil and there are at least seventeen species distributed in nine genera. Some of these plants have well known toxic compounds; in others, the substance responsible for the disease is unknown. In general, the photosensitivity can be classified as primary or secondary. Among the plants causing primary photosensitivity in Brazil, Ammi majus contains furocoumarins, while the compound in Froelichia humboldtiana remains uncertain. The known toxic compounds causing secondary photosensitivity include pyrrolizidine alkaloids, furans sesquiterpenes, triterpenes, and steroidal saponins. In other plants causing secondary photosensitization, including Stryphnodendron spp. and Enterolobium spp., the toxic compound is still unknown. Future research should be conducted in order to determine the various mechanisms of action of each toxic compound to assist the diagnosis of photosensitivity, to develop less toxic or non-toxic cultivars, or even to find new ways of preventing photosensitization.

scholarly journals The emerging role of lactate as a mediator of exercise-induced appetite suppression

2020 ◽  
Vol 319 (4) ◽  
pp. E814-E819
Author(s):  
Seth F. McCarthy ◽  
Hashim Islam ◽  
Tom J. Hazell
Keyword(s):  
Overweight And Obesity ◽  
Future Research ◽  
Ghrelin Receptor ◽  
Cellular Models ◽  
Regulatory Molecule ◽  
Blood Lactate Accumulation ◽  
Underlying Mechanisms ◽  
Exercise Induced

Lactate, a molecule originally considered metabolic waste, is now associated with a number of important physiological functions. Although the roles of lactate as a signaling molecule, fuel source, and gluconeogenic substrate have garnered significant attention in recent reviews, a relatively underexplored and emerging role of lactate is its control of energy intake (EI). To expand our understanding of the physiological roles of lactate, we present evidence from early infusion studies demonstrating the ability of lactate to suppress EI in both rodents and humans. We then discuss findings from recent human studies that have utilized exercise intensity and/or sodium bicarbonate supplementation to modulate endogenous lactate and examine its impact on appetite regulation. These studies consistently demonstrate that greater blood lactate accumulation is associated with greater suppression of the hunger hormone ghrelin and subjective appetite, thereby supporting a role of lactate in the control of EI. To stimulate future research investigating the role of lactate as an appetite-regulatory molecule, we also highlight potential underlying mechanisms explaining the appetite-suppressive effects of lactate using evidence from rodent and in vitro cellular models. Specifically, we discuss the ability of lactate to 1) inhibit the secretory function of ghrelin producing gastric cells, 2) modulate the signaling cascades that control hypothalamic neuropeptide expression/release, and 3) inhibit signaling through the ghrelin receptor in the hypothalamus. Unravelling the role of lactate as an appetite-regulatory molecule can shed important insight into the regulation of EI, thereby contributing to the development of interventions aimed at combatting overweight and obesity.

scholarly journals The claustrum: Considerations regarding its anatomy, functions and a programme for research

2017 ◽  
Vol 1 ◽  
pp. 239821281771896 ◽  
Author(s):  
Christopher M. Dillingham ◽  
Maciej M. Jankowski ◽  
Ruchi Chandra ◽  
Bethany E. Frost ◽  
Shane M. O’Mara
Keyword(s):  
Decision Making ◽  
Information Processing ◽  
Brain Region ◽  
Spatial Information ◽  
Mammalian Brain ◽  
Future Research ◽  
Subcortical Structures ◽  
Present Evidence ◽  
Open Questions ◽  
Extensive Range

The claustrum is a highly conserved but enigmatic structure, with connections to the entire cortical mantle, as well as to an extended and extensive range of heterogeneous subcortical structures. Indeed, the human claustrum is thought to have the highest number of connections per millimetre cubed of any other brain region. While there have been relatively few functional investigations of the claustrum, many theoretical suggestions have been put forward, including speculation that it plays a key role in the generation of consciousness in the mammalian brain. Other claims have been more circumspect, suggesting that the claustrum has a particular role in, for example, orchestrating cortical activity, spatial information processing or decision making. Here, we selectively review certain key recent anatomical, electrophysiological and behavioural experimental advances in claustral research and present evidence that calls for a reassessment of its anatomical boundaries in the rodent. We conclude with some open questions for future research.

scholarly journals Brain Aging in the Oldest-Old

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
A. von Gunten ◽  
K. Ebbing ◽  
A. Imhof ◽  
P. Giannakopoulos ◽  
E. Kövari
Keyword(s):  
Brain Aging ◽  
Hippocampal Formation ◽  
Anterior Part ◽  
Oldest Old ◽  
Senile Plaques ◽  
Temporal Cortex ◽  
Clinical Signs ◽  
Neuronal Loss ◽  
Future Research ◽  
Cornu Ammonis

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to “longevity-enabling” genes although little or nothing is known in this promising field of future research.

scholarly journals Vasopressin excites interneurons to suppress hippocampal network activity across a broad span of brain maturity at birth

2017 ◽  
Vol 114 (50) ◽  
pp. E10819-E10828 ◽  
Author(s):  
Albert Spoljaric ◽  
Patricia Seja ◽  
Inkeri Spoljaric ◽  
Mari A. Virtanen ◽  
Jenna Lindfors ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Arginine Vasopressin ◽  
Oxygen Supply ◽  
Stress Hormones ◽  
Network Activity ◽  
Mammalian Brain ◽  
Protective Effects ◽  
Evolutionarily Conserved ◽  
Hippocampal Network

During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABAA receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth.

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