Article
Clinical Neurology
Claire O'Callaghan, Frank H. Hezemans, Rong Ye, Catarina Rua, P. Simon Jones, Alexander G. Murley, Negin Holland, Ralf Regenthal, Kamen A. Tsvetanov, Noham Wolpe, Roger A. Barker, Caroline H. Williams-Gray, Trevor W. Robbins, Luca Passamonti, James B. Rowe
Summary: Cognitive decline is common in Parkinson's disease and often unresponsive to dopaminergic therapy. Targeting the locus coeruleus-noradrenaline system may improve response inhibition deficits, with atomoxetine showing potential in some patients. Predicting treatment response and patient selection for atomoxetine therapy based on locus coeruleus integrity is crucial for optimizing therapeutic outcomes.
Review
Clinical Neurology
Negin Holland, Trevor W. Robbins, James B. Rowe
Summary: This review highlights the important role of noradrenergic projections from the locus coeruleus in regulating cognition and behavior, as well as their loss in neurodegenerative diseases. Advances in human imaging and computational methods for quantifying the locus coeruleus and potential new noradrenergic treatment strategies are also discussed.
Article
Clinical Neurology
Benjamin Huynh, Yuhong Fu, Deniz Kirik, James M. Shine, Glenda M. Halliday
Summary: The study compared cell loss in different brain regions of Parkinson's disease patients and found that the loss of noradrenergic A6 locus coeruleus neurons did not strictly follow a caudal to rostral trajectory in the same cases. Pathological onset in the noradrenergic A6 locus coeruleus may relate to symptom onset in people with reduced dopamine-producing A9 substantia nigra neurons.
MOVEMENT DISORDERS
(2021)
Article
Anesthesiology
Carmen Camarena-Delgado, Meritxell Llorca-Torralba, Irene Suarez-Pereira, Lidia Bravo, Carolina Lopez-Martin, Jose A. Garcia-Partida, Juan A. Mico, Esther Berrocoso
Summary: The transition from acute to chronic pain leads to maladaptive brain remodeling and sensory hypersensitivity. This study found time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury and discovered the involvement of the LC -> dorsal reticular nucleus (DRt) pathway in chronic pain. Lidocaine blockade of LC ipsilateral to the lesion increased cold allodynia and reversed pain-induced depression. Inactivation of the LCcontra -> DRt(contra) pathway produced consistent analgesia in chronic pain and induced depressive-like behavior in naive animals.
Article
Clinical Neurology
Christopher F. Madelung, David Meder, Soren A. Fuglsang, Marta M. Marques, Vincent O. Boer, Kristoffer H. Madsen, Esben T. Petersen, Anne-Mette Hejl, Annemette Lokkegaard, Hartwig R. Siebner
Summary: This study used neuromelanin sensitive magnetic resonance imaging (MRI) to examine the structural disintegration of the locus coeruleus (LC) and its association with nonmotor dysfunction in patients with Parkinson's disease (PD). The findings showed that PD patients had reduced structural integrity in the right LC, specifically in the mid-caudal region. The disintegration of the LC was linked to specific nonmotor symptoms, such as orthostatic dysregulation and apathy. Additionally, the severity of nonmotor symptoms was associated with the overall structural disintegration of the LC.
MOVEMENT DISORDERS
(2022)
Article
Cell Biology
Nicolo Gabriele Pozzi, Francesco Bolzoni, Gabriele Eliseo Mario Biella, Gianni Pezzoli, Chi Wang Ip, Jens Volkmann, Paolo Cavallari, Esther Asan, Ioannis Ugo Isaias
Summary: This study investigated the development of tremor in Parkinson's disease (PD) using a rat model with selective lesioning of LC-NA innervation. The results showed that LC-NA innervation plays a critical role in the development of PD tremor.
Review
Physiology
Eus J. W. Van Someren
Summary: Insomnia is the second most common mental disorder, yet progress in understanding its underlying neurobiological mechanisms has been limited. This review explores the definition, prevalence, and susceptibility factors of insomnia, including genetic variants, early life stress, major life events, and brain structure and function. The proposed model suggests that in individuals vulnerable to developing insomnia, the locus coeruleus may be more sensitive to salience network input, leading to a spiral of hyperarousal and impaired sleep.
PHYSIOLOGICAL REVIEWS
(2021)
Editorial Material
Neurosciences
Juan Facundo Morici, Gabrielle Girardeau
Summary: A new study reveals that infra-slow cortical norepinephrine oscillations play a crucial role in shaping the micro-structure of sleep and transitions between wakefulness, micro-arousals, and REM sleep. Furthermore, prolonged descending phases of these oscillations enhance the occurrence of spindle-rich intermediate sleep, which is involved in memory consolidation.
NATURE NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Toshiharu Nagatsu, Akira Nakashima, Hirohisa Watanabe, Shosuke Ito, Kazumasa Wakamatsu
Summary: Parkinson's disease is an aging-related neurodegenerative disease characterized by movement disorders and deficiency of dopamine. Lewy bodies and abnormal accumulation of neuromelanin are the histopathological hallmarks of Parkinson's disease, leading to cell death of dopamine neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Michelle J. Chandley, Attila Szebeni, Katalin Szebeni, Hui Wang-Heaton, Jacob Garst, Craig A. Stockmeier, Nicole H. Lewis, Gregory A. Ordway
Summary: Major depressive disorder (MDD) and suicide are associated with oxidative damage and white matter pathology in the brain, particularly in the oligodendrocytes. This study found that oligodendrocyte pathology related to oxidative damage extends to brain areas outside of those traditionally associated with MDD and suicide psychopathology.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Review
Clinical Neurology
Camille Malatt, Michele Tagliati
Summary: This review provides an update on the current understanding of the neuropathological processes affecting the locus coeruleus/norepinephrine (LC/NE) system and their impact on the symptomatology of Alzheimer's disease and Parkinson's disease. It also explores therapeutic actions targeting the noradrenergic system. Recent studies have shown that locus coeruleus degeneration and/or hyperactivation play an early role in the neurodegenerative process, including triggering neuroinflammation. Nonmotor and noncognitive symptoms, associated with the involvement of the LC/NE system, have become increasingly important in the definition and treatment of these diseases. The diverse symptomatology of Alzheimer's disease and Parkinson's disease suggests a multisystem neurodegenerative process, with the LC/NE system playing a key role in its initiation and maintenance.
CURRENT OPINION IN NEUROLOGY
(2022)
Review
Neurosciences
Anouk Tosserams, Bastiaan R. Bloem, Kaylena Ehgoetz A. Martens, Rick C. Helmich, Roy P. C. Kessels, James M. Shine, Natasha L. Taylor, Gabriel Wainstein, Simon J. G. Lewis, Jorik Nonnekes
Summary: In stressful situations, individuals with Parkinson's disease (PD) may experience worsening of motor symptoms, including gait impairments. However, some patients report benefits from stressful or high-arousal situations. A study with 4324 PD patients shows that they use various mental strategies to cope with gait impairments, which can either increase or decrease overall sympathetic tone. This suggests that arousal can have both detrimental and alleviating effects on gait control in PD.
TRANSLATIONAL NEURODEGENERATION
(2023)
Review
Pharmacology & Pharmacy
Andrew K. Evans, Erwin Defensor, Mehrdad Shamloo
Summary: This review examines the vulnerability mechanisms of locus coeruleus noradrenergic neurons, the impact of environmental and genetic factors on their risk, and potential interventions to reduce degeneration of these neurons.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Qiang Tong, Liam Chen
Summary: Neuropathological changes in Alzheimer's disease significantly increase the risk of hallucinations and dementia in Parkinson's disease patients, while diffuse Lewy body pathology is associated with the occurrence of these symptoms. Interestingly, neuronal loss in the locus coeruleus is found to contribute to dyskinesia in advanced Parkinson's disease patients. Understanding the relationships between these different pathologies and their clinical phenotypes is crucial for the development of effective therapies for PD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neuroimaging
Xinhui Wang, Pei Huang, Ewart Mark Haacke, Yu Liu, Youmin Zhang, Zhijia Jin, Yan Li, Qiuyun Xu, Peng Liu, Shengdi Chen, Naying He, Fuhua Yan
Summary: Neuromelanin measures of the substantia nigra and locus coeruleus can improve the differential diagnosis of essential tremor and Parkinson's disease. There are significant differences in neuromelanin measures between patients with Parkinson's disease and those with essential tremor or healthy controls. Utilizing these measures for differential diagnosis can achieve high accuracy.
NEUROIMAGE-CLINICAL
(2023)
