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International Journal of Molecular... Nov 2017Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are used to treat chronic pain, such as neuropathic pain. Why antidepressants are effective for... (Review)
Review
Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are used to treat chronic pain, such as neuropathic pain. Why antidepressants are effective for treatment of neuropathic pain and the precise mechanisms underlying their effects, however, remain unclear. The inhibitory effects of these antidepressants for neuropathic pain manifest more quickly than their antidepressive effects, suggesting different modes of action. Recent studies of animal models of neuropathic pain revealed that noradrenaline is extremely important for the inhibition of neuropathic pain. First, increasing noradrenaline in the spinal cord by reuptake inhibition directly inhibits neuropathic pain through α₂-adrenergic receptors. Second, increasing noradrenaline acts on the locus coeruleus and improves the function of an impaired descending noradrenergic inhibitory system. Serotonin and dopamine may reinforce the noradrenergic effects to inhibit neuropathic pain. The mechanisms of neuropathic pain inhibition by antidepressants based mainly on experimental findings from animal models of neuropathic pain are discussed in this review.
Topics: Analgesics; Animals; Antidepressive Agents; Depression; Dopamine; Humans; Locus Coeruleus; Neuralgia; Norepinephrine; Serotonin; Spinal Cord
PubMed: 29160850
DOI: 10.3390/ijms18112483 -
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 -
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 -
Brain : a Journal of Neurology Mar 2022There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining...
There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi→spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.
Topics: Animals; Comorbidity; Depression; Humans; Locus Coeruleus; Neuralgia; Neurons; Rats
PubMed: 34373893
DOI: 10.1093/brain/awab239 -
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 -
Frontiers in Endocrinology 2023is a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways.... (Review)
Review
is a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the gene encompass fibrous dysplasia (FD), Albright's Hereditary Osteodystrophy (AHO), parathyroid hormone(PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases.
Topics: Animals; Mice; Humans; GTP-Binding Protein alpha Subunits, Gs; Chromogranins; Pseudohypoparathyroidism; Bone Diseases, Metabolic; Ossification, Heterotopic
PubMed: 37920253
DOI: 10.3389/fendo.2023.1255864 -
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 -
Brain : a Journal of Neurology Sep 2021Many aspects of cognition and behaviour are regulated by noradrenergic projections to the forebrain originating from the locus coeruleus, acting through alpha and beta... (Review)
Review
Many aspects of cognition and behaviour are regulated by noradrenergic projections to the forebrain originating from the locus coeruleus, acting through alpha and beta adrenoreceptors. Loss of these projections is common in neurodegenerative diseases and contributes to their cognitive and behavioural deficits. We review the evidence for a noradrenergic modulation of cognition in its contribution to Alzheimer's disease, Parkinson's disease and other cognitive disorders. We discuss the advances in human imaging and computational methods that quantify the locus coeruleus and its function in humans, and highlight the potential for new noradrenergic treatment strategies.
Topics: Cognition; Cognition Disorders; Humans; Locus Coeruleus; Norepinephrine
PubMed: 33725122
DOI: 10.1093/brain/awab111 -
Journal of Biological Inorganic... Dec 2019Copper (Cu) plays an essential role in the development and function of the brain. In humans, genetic disorders of Cu metabolism may cause either severe Cu deficiency... (Review)
Review
Copper (Cu) plays an essential role in the development and function of the brain. In humans, genetic disorders of Cu metabolism may cause either severe Cu deficiency (Menkes disease) or excessive Cu accumulation (Wilson disease) in the brain tissue. In either case, the loss of Cu homeostasis results in catecholamine misbalance, abnormal myelination of neurons, loss of normal brain architecture, and a spectrum of neurologic and/or psychiatric manifestations. Several metabolic processes have been identified as particularly sensitive to Cu dis-homeostasis. This review focuses on the role of Cu in noradrenergic neurons and summarizes the current knowledge of mechanisms that maintain Cu homeostasis in these cells. The impact of Cu misbalance on catecholamine metabolism and functioning of noradrenergic system is discussed.
Topics: Adrenergic Neurons; Animals; Catecholamines; Copper; Homeostasis; Humans; Ion Transport; Locus Coeruleus
PubMed: 31691104
DOI: 10.1007/s00775-019-01737-3