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Cell and Tissue Research Jul 2018The locus coeruleus (LC) contains norepinephrine (NE)-synthesizing neurons that send diffuse projections throughout the central nervous system. The LC-NE system has a... (Review)
Review
The locus coeruleus (LC) contains norepinephrine (NE)-synthesizing neurons that send diffuse projections throughout the central nervous system. The LC-NE system has a major role in arousal, attention and stress responses. In the brain, NE may also contribute to long-term synaptic plasticity, pain modulation, motor control, energy homeostasis and control of local blood flow. The LC is severely affected in neurodegenerative disorders including Parkinson disease (PD). Involvement of the noradrenergic neurons of the LC precedes that of dopaminergic neurons of the substantia nigra pars compacta and has been increasingly recognized as a potential major contributor to cognitive manifestations in early PD, particularly impaired attention. Abnormal noradrenergic signaling may also potentially contribute to motor manifestations of the disease.This makes the LC-NE system a major contributor to the pathobiology and potential target for therapy of PD.
Topics: Animals; Disease Models, Animal; Dopaminergic Neurons; Humans; Locus Coeruleus; Norepinephrine; Parkinson Disease
PubMed: 28687925
DOI: 10.1007/s00441-017-2649-1 -
Current Biology : CB Nov 2015The release of the neurotransmitter norepinephrine throughout the mammalian brain is important for modulating attention, arousal, and cognition during many behaviors.... (Review)
Review
The release of the neurotransmitter norepinephrine throughout the mammalian brain is important for modulating attention, arousal, and cognition during many behaviors. Furthermore, disruption of norepinephrine-mediated signaling is strongly associated with several psychiatric and neurodegenerative disorders in humans, emphasizing the clinical importance of this system. Most of the norepinephrine released in the brain is supplied by a very small, bilateral nucleus in the brainstem called the locus coeruleus. The goal of this minireview is to emphasize the complexity of the locus coeruleus beyond its primary definition as a norepinephrine-producing nucleus. Several recent studies utilizing innovative technologies highlight how the locus coeruleus-norepinephrine system can now be targeted with increased accuracy and resolution, in order to better understand its role in modulating diverse behaviors.
Topics: Animals; Attention; Brain; Brain Stem; Cognition; Humans; Locus Coeruleus; Norepinephrine
PubMed: 26528750
DOI: 10.1016/j.cub.2015.09.039 -
Frontiers in Neuroscience 2022Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson's disease. The mechanism by which this... (Review)
Review
Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson's disease. The mechanism by which this locus modulates the disease pathology and etiology remains largely under-investigated. This is due to the assumption that is the only driver of the functional aspects of several single nucleotide polymorphism (SNP) risk-signals at this locus. Recent evidence has shown that the risk associated with the top GWAS-identified variant within this locus is independent of expression, calling into question the validity of assigning function to the nearest gene, . In this review, we examine additional genes and risk variants present at the locus and how they may contribute to Parkinson's disease. Using the locus as an example, we hope to demonstrate that deeper and detailed functional validations are required for high impact disease-linked variants.
PubMed: 35898413
DOI: 10.3389/fnins.2022.889802 -
Optics Express Apr 2022In this paper, directly following from Gage [J. Opt. Soc. Am.23, 46(1993)10.1364/JOSA.23.000046], we study the design of a particular theoretical filter for photography,...
In this paper, directly following from Gage [J. Opt. Soc. Am.23, 46(1993)10.1364/JOSA.23.000046], we study the design of a particular theoretical filter for photography, that we call the locus filter. It is built in such a way that a Wien-Planckian light (of any temperature) is spectrally mapped to another Wien-Planckian light. We provide a physical basis for designing such a filter based on the Wien approximation of Planck's law, and we prove that there exists a unique set of filters that have the desired property. While locus filtered Wien-Planckian lights are on the locus, the amount they shift depends both on the locus filter used and on the color temperature of the light. In experiments, we analyze the nature of temperature change when applying different locus filters and we show that real lights shift more or less as if they were Planckians in terms of the changes in their correlated color temperatures. We also study the quality of the filtered light in terms of distance from the Planckian locus and color rendering index.
PubMed: 35472916
DOI: 10.1364/OE.448160 -
Proceedings of the National Academy of... Nov 2021The last decade has seen significant progress identifying genetic and brain differences related to intelligence. However, there remain considerable gaps in our... (Review)
Review
The last decade has seen significant progress identifying genetic and brain differences related to intelligence. However, there remain considerable gaps in our understanding of how cognitive mechanisms that underpin intelligence map onto various brain functions. In this article, we argue that the locus coeruleus-norepinephrine system is essential for understanding the biological basis of intelligence. We review evidence suggesting that the locus coeruleus-norepinephrine system plays a central role at all levels of brain function, from metabolic processes to the organization of large-scale brain networks. We connect this evidence with our executive attention view of working-memory capacity and fluid intelligence and present analyses on baseline pupil size, an indicator of locus coeruleus activity. Using a latent variable approach, our analyses showed that a common executive attention factor predicted baseline pupil size. Additionally, the executive attention function of disengagement--not maintenance--uniquely predicted baseline pupil size. These findings suggest that the ability to control attention may be important for understanding how cognitive mechanisms of fluid intelligence map onto the locus coeruleus-norepinephrine system. We discuss how further research is needed to better understand the relationships between fluid intelligence, the locus coeruleus-norepinephrine system, and functionally organized brain networks.
Topics: Animals; Attention; Brain; Executive Function; Humans; Individuality; Intelligence; Locus Coeruleus; Memory, Short-Term; Norepinephrine; Pupil
PubMed: 34764223
DOI: 10.1073/pnas.2110630118 -
Expert Review of Respiratory Medicine Sep 2017The imprinted DLK1-DIO3 locus at 14q32.1-32.31 holds biological significance in fetal development, whereby imprinting errors are causal to developmental disorders.... (Review)
Review
The imprinted DLK1-DIO3 locus at 14q32.1-32.31 holds biological significance in fetal development, whereby imprinting errors are causal to developmental disorders. Emerging evidence has implicated this locus in other diseases including cancer, highlighting the biological parallels between fetal organ and tumour development. Areas covered: Controlled regulation of gene expression from the imprinted DLK1-DIO3 locus at 14q32.1-32.31 is crucial for proper fetal development. Deregulation of locus gene expression due to imprinting errors has been mechanistically linked to the developmental disorders Kagami-Ogata Syndrome and Temple Syndrome. In adult tissues, deregulation of locus genes has been associated with multiple malignancies although the causal genetic mechanisms remain largely uncharacterised. Here, we summarize the genetic mechanisms underlying the developmental disorders that arise as a result of improper locus imprinting and the resulting developmental phenotypes, emphasizing both the coding and noncoding components of the locus. We further highlight biological parallels common to both fetal development and disease, with a specific focus on lung development, respiratory disease, and lung cancer. Expert commentary: Many commonalities between respiratory and developmental defects have emerged with respect to the 14q32 locus, emphasizing the importance of studying the effects of imprinting on gene regulation patterns at this locus in both biological settings.
Topics: Animals; Calcium-Binding Proteins; Chromosomes, Human, Pair 14; Fetal Development; Genomic Imprinting; Humans; Intercellular Signaling Peptides and Proteins; Iodide Peroxidase; Membrane Proteins; Neoplasms; Phenotype; Respiration Disorders; Uniparental Disomy
PubMed: 28715922
DOI: 10.1080/17476348.2017.1355241 -
International Journal of Environmental... Jan 2023Alzheimer's disease (AD) is a leading neurodegenerative disease with deteriorating cognition as its main clinical sign. In addition to the clinical history, it is... (Review)
Review
Alzheimer's disease (AD) is a leading neurodegenerative disease with deteriorating cognition as its main clinical sign. In addition to the clinical history, it is characterized by the presence of two neuropathological hallmark lesions; amyloid-beta (Aβ) and neurofibrillary tangles (NFTs), identified in the brain at post-mortem in specific anatomical areas. Recently, it was discovered that NFTs occur initially in the subcortical nuclei, such as the locus coeruleus in the pons, and are said to spread from there to the cerebral cortices and the hippocampus. This contrasts with the prior acceptance of their neuropathology in the enthorinal cortex and the hippocampus. The Braak staging system places the accumulation of phosphorylated tau (p-tau) binding to NFTs in the locus coeruleus and other subcortical nuclei to precede stages I-IV. The locus coeruleus plays diverse psychological and physiological roles within the human body including rapid eye movement sleep disorder, schizophrenia, anxiety, and depression, regulation of sleep-wake cycles, attention, memory, mood, and behavior, which correlates with AD clinical behavior. In addition, the locus coeruleus regulates cardiovascular, respiratory, and gastrointestinal activities, which have only recently been associated with AD by modern day research enabling the wider understanding of AD development via comorbidities and microbial dysbiosis. The focus of this narrative review is to explore the modes of neurodegeneration taking place in the locus coeruleus during the natural aging process of the trigeminal nerve connections from the teeth and microbial dysbiosis, and to postulate a pathogenetic mechanism due to periodontal damage and/or infection focused on .
Topics: Humans; Alzheimer Disease; Locus Coeruleus; tau Proteins; Neurodegenerative Diseases; Cues; Dysbiosis; Periodontitis
PubMed: 36673763
DOI: 10.3390/ijerph20021007 -
Frontiers in Psychology 2020Having an external locus of control has been associated with a range of well-supported risk correlates of offending behavior. Further, individuals with an internal locus... (Review)
Review
Having an external locus of control has been associated with a range of well-supported risk correlates of offending behavior. Further, individuals with an internal locus of control orientation are suggested to be more open to engaging in treatment and are also considered more likely to have successful treatment outcomes. In forensic settings, where individuals are subject to external controls and have little personal autonomy, it is important to consider what treatment approaches might be most successful in reorienting individuals' locus of control. The Good Lives Model (GLM) proposes a strengths-based approach to the rehabilitation of individuals who have offended. Within the GLM, an external locus of control is suggested to be associated with a deficit in the primary good of agency. In this article, we will provide a brief overview of the literature on locus of control and its hypothesized role in offending behavior. We will discuss how an external locus of control orientation is related to personal agency and how strengths-based models, such as the GLM, may assist with reorienting locus of control in individuals who have offended through promoting personal agency.
PubMed: 33041920
DOI: 10.3389/fpsyg.2020.553240 -
The International Journal of... Mar 2020Noradrenergic system of brain supplies the neurotransmitter noradrenalin throughout the brain through widespread efferent projections and play pivotal role in cognitive... (Review)
Review
Noradrenergic system of brain supplies the neurotransmitter noradrenalin throughout the brain through widespread efferent projections and play pivotal role in cognitive activities and could be involve in motor and non-motor symptoms of Parkinson's disease (PD) pathology. Profound loss of noradrenergic pathways has been reported in both Parkinson's and Alzheimer's disease (AD) pathology however their employment in therapeutics is still scarce. Therefore the present review is providing the various aspects for involvement on noradrenergic pathways in PD and AD pathology as well as the imaging of locus coeruleus as indicative diagnostic marker for disease. The present review is describing about the role of tiny nucleus locus coeruleus located noradrenergic pathways in said pathologies and discussing the past research as well as lacunas in this regard.
Topics: Alzheimer Disease; Humans; Locus Coeruleus; Neural Pathways; Norepinephrine; Parkinson Disease; Signal Transduction
PubMed: 31575316
DOI: 10.1080/00207454.2019.1667799