Locus coeruleus: a new look at the blue spot

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(11), P. 644 - 659

Published: Sept. 17, 2020

Language: Английский

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Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases

Brain, Journal Year: 2019, Volume and Issue: 142(9), P. 2558 - 2571

Published: June 11, 2019

Abstract Pathological alterations to the locus coeruleus, major source of noradrenaline in brain, are histologically evident early stages neurodegenerative diseases. Novel MRI approaches now provide an opportunity quantify structural features coeruleus vivo during disease progression. In combination with neuropathological biomarkers, imaging could help understand contribution neurodegeneration clinical and pathological manifestations Alzheimer’s disease, atypical dementias Parkinson’s disease. Moreover, as functional sensitivity noradrenergic system is likely change progression, measures integrity new pathophysiological insights into cognitive behavioural symptoms. Locus also holds promise stratify patients trials according dysfunction. this article, we present a consensus on how non-invasive assessment can be used for research We outline next steps vivo, post-mortem studies that lay groundwork evaluate potential biomarker

Language: Английский

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Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation

Neuron, Journal Year: 2019, Volume and Issue: 103(4), P. 702 - 718.e5

Published: June 18, 2019

Language: Английский

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Rostral locus coeruleus integrity is associated with better memory performance in older adults

Nature Human Behaviour, Journal Year: 2019, Volume and Issue: 3(11), P. 1203 - 1214

Published: Sept. 9, 2019

Language: Английский

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Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2018, Volume and Issue: 66(1), P. 115 - 126

Published: Sept. 7, 2018

Clarifying the relationships between neuropsychiatric symptoms and Alzheimer’s disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate odds of developing across increasing burdens neurofibrillary tangle amyloid-β pathology. Participants who passed away 2004 2014 underwent comprehensive neuropathologic evaluation at Biobank Aging Studies from Faculty Medicine University São Paulo. Postmortem interviews with reliable informants were used to collect information regarding cognitive status. Of 1,092 cases collected, those any non-Alzheimer excluded, bringing cohort 455 cases. Braak staging was evaluate burden, CERAD neuropathology score burden. The 12-item inventory CDR-SOB dementia In I/II, significantly increased detected agitation, anxiety, appetite changes, depression, sleep disturbances, compared controls. Increased agitation continue into III/IV. V/VI is associated higher delusions. No found correlate are early pathology, suggesting that subcortical accumulation minimal cortical sufficient impact quality life a manifestation AD biological processes.

Language: Английский

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Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(11), P. 5108 - 5117

Published: Feb. 22, 2019

Significance Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product dopamine metabolism that accumulates in substantia nigra (SN). Prior work has shown NM-MRI provides marker SN integrity Parkinson’s disease. Here, we show it may additionally provide function human nigrostriatal pathway. Supporting this, found signal correlated with NM concentration, levels striatum, blood flow, and severity psychosis schizophrenia, all absence neurodegeneration. Thus, noninvasive is promising tool could have diverse research clinical applications investigate vivo role neuropsychiatric illness.

Language: Английский

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The mechanistic link between selective vulnerability of the locus coeruleus and neurodegeneration in Alzheimer’s disease

Acta Neuropathologica, Journal Year: 2021, Volume and Issue: 141(5), P. 631 - 650

Published: Jan. 11, 2021

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the intracellular accumulation of hyperphosphorylated tau and extracellular deposition amyloid-β plaques, which affect certain brain regions in a progressive manner. The locus coeruleus (LC), small nucleus pons brainstem, widely recognized as one earliest sites neurofibrillary tangle formation AD. Patients with AD exhibit significant neuronal loss LC, resulting marked reduction its size function. vastly innervates several brain, primary source neurotransmitter norepinephrine (NE) central nervous system. Considering that NE major modulator behavior, contributing to neuroprotection suppression neuroinflammation, degeneration LC ultimate dysregulation LC–NE system has detrimental effects brain. In this review, we detail neuroanatomy function essential role neuroprotection, how dysregulated We discuss AD-related neuropathologic changes mechanisms neurons are selectively vulnerable insult. Further, elucidate neurotoxic de-innervation both locally at projection sites, augments pathology, progression severity. summarize preservation could be used treatment other neurodegenerative diseases affected degeneration.

Language: Английский

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The Cholinergic System, the Adrenergic System and the Neuropathology of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(3), P. 1273 - 1273

Published: Jan. 28, 2021

Neurodegenerative diseases are a major public health problem worldwide with wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation cholinergic system adrenergic linked to etiology Alzheimer's disease. Cholinergic neurons widely distributed in brain regions play role cognitive functions normal signaling related learning memory is dependent on acetylcholine. The Locus Coeruleus norepinephrine (LC-NE) main noradrenergic nucleus projects supplies different regions. Norepinephrine shown be neuroprotective against neurodegeneration plays behavior cognition. dysregulated degeneration basalis Meynert basal forebrain LC-NE were aim this review describe current literature pathology disease potential therapeutic implications.

Language: Английский

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Neurobiology of depression in Parkinson’s disease: Insights into epidemiology, molecular mechanisms and treatment strategies

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 85, P. 101840 - 101840

Published: Jan. 2, 2023

Language: Английский

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Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure

Science Advances, Journal Year: 2025, Volume and Issue: 11(3)

Published: Jan. 17, 2025

Homeostatic sleep regulation is essential for optimizing the amount and timing of its revitalizing function, but mechanism underlying homeostasis remains poorly understood. Here, we show that optogenetic activation locus coeruleus (LC) noradrenergic neurons immediately increased propensity following a transient wakefulness, contrasting with many other arousal-promoting whose induces sustained wakefulness. Fiber photometry showed repeated or sensory stimulation caused rapid reduction calcium activity in LC steep declines noradrenaline/norepinephrine (NE) release both medial prefrontal cortex (mPFC). Knockdown α 2 A adrenergic receptors mitigated decline NE induced by repetitive extended demonstrating an important role receptor–mediated auto-suppression release. Together, these results suggest functional fatigue neurons, which reduces their wake-promoting capacity, contributes to pressure.

Language: Английский

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