Fading Blue: Exploring the Causes of Locus Coeruleus Damage Across the Lifespan DOI Creative Commons
Alessandro Galgani,

Marco Scotto,

Ugo Faraguna

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 255 - 255

Published: Feb. 22, 2025

Locus Coeruleus (LC) is a brain nucleus that involved in variety of key functions (ranging from attention modulation to sleep-wake cycle regulation, memory encoding); its proper function necessary both during development and for integrity maintenance, at the microscale macroscale level. Due their specific intrinsic extrinsic features, LC cells are considered particularly susceptible damage concerning insults. This explains involvement degenerative diseases not only adults (in context neurodegenerative disease, mainly), but also children relation early hypoxic Down's Syndrome, among others). In this narrative review, we dissect potential mechanisms through which affected different diseases, with special emphasis on high rate activity it subjected oxidative stress associated it. Further research aimed deepening our understanding these needed enable strategies future could slow down degeneration subjects predisposed disorders.

Language: Английский

Biological effects of pathologies in Lewy body diseases: why timing matters DOI
Elie Matar, Glenda M. Halliday

The Lancet Neurology, Journal Year: 2025, Volume and Issue: 24(5), P. 441 - 455

Published: April 16, 2025

Language: Английский

Citations

1
Role of dopamine and clinical heterogeneity in cognitive dysfunction in Parkinson's disease DOI
Roshan Cools, Jorryt Tichelaar, Rick C. Helmich

et al.

Progress in brain research, Journal Year: 2022, Volume and Issue: unknown, P. 309 - 343

Published: Jan. 1, 2022

Language: Английский

Citations

27
Application of Neuromelanin MR Imaging in Parkinson Disease DOI Creative Commons
Naying He, Yongsheng Chen, Peter A. LeWitt

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2022, Volume and Issue: 57(2), P. 337 - 352

Published: Aug. 26, 2022

MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative with parkinsonism progressive supranuclear palsy multiple system atrophy. One of these imaging is neuromelanin (NM), whose integrity can be assessed from its contrast volume. NM found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), ventral tegmental area, locus coeruleus. Another major biomarker iron, which often increases concert degeneration. These have potential improve diagnostic certainty differentiating between PD similar PD, well provide a better understanding pathophysiology. Mapping vivo clinical importance gauging premotor phase when there greater than 50% loss dopaminergic SNpc melanized neurons. As metal ion chelator, absorb iron. When released neurons, it deposits iron into intracellular tissues SNpc; result that imaged measured using quantitative susceptibility mapping. An increase also leads disappearance nigrosome‐1 sign, another neuroimage PD. Therefore, mapping changes are practical means improving early diagnosis monitoring progression. In this review, we discuss functions location NM, how NM‐MRI performed, automatic content, NM‐related enhance differentiate disorders, advances methods. With currently evolving rapid artificial intelligence, likely increasingly important roles enhancing capabilities Evidence Level 1 Technical Efficacy Stage 2

Language: Английский

Citations

25
The Neurotoxin DSP-4 Dysregulates the Locus Coeruleus-Norepinephrine System and Recapitulates Molecular and Behavioral Aspects of Prodromal Neurodegenerative Disease DOI Creative Commons

Alexa F. Iannitelli,

Michael A. Kelberman, Daniel J. Lustberg

et al.

eNeuro, Journal Year: 2022, Volume and Issue: 10(1), P. ENEURO.0483 - 22.2022

Published: Dec. 9, 2022

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) Parkinson's (PD), respectively. onset these pathologies coincides with loss fibers LC target regions emergence prodromal symptoms including sleep disturbances anxiety. Paradoxically, are indicative a hyperactivity phenotype, rather than predicted norepinephrine (NE) transmission following damage, suggesting engagement complex compensatory mechanisms. Because current therapeutic efforts targeting early disease, interest has grown, it critical to identify links between dysfunction. We employed LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which preferentially damages axons, model changes LC-NE system pertinent AD PD male female mice. DSP-4 (two doses 50 mg/kg, one week apart) induced axon degeneration, triggered neuroinflammation oxidative stress, reduced tissue NE levels. There was no cell death or firing, but transcriptomics revealed expression genes that define identity other relevant neurodegenerative disease. Despite dramatic fibers, turnover signaling were elevated terminal associated anxiogenic phenotypes multiple behavioral tests. These results represent comprehensive analysis how responds axon/terminal damage reminiscent at molecular, cellular, systems, levels, provides potential mechanisms underlying neuropsychiatric symptoms.

Language: Английский

Citations

23
Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons DOI Creative Commons

Alexa F. Iannitelli,

David Weinshenker

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105287 - 105287

Published: June 15, 2023

Language: Английский

Citations

15
Modulating arousal to overcome gait impairments in Parkinson’s disease: how the noradrenergic system may act as a double-edged sword DOI Creative Commons
Anouk Tosserams, Bastiaan R. Bloem, Kaylena A. Ehgoetz Martens

et al.

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: March 26, 2023

Abstract In stressful or anxiety-provoking situations, most people with Parkinson’s disease (PD) experience a general worsening of motor symptoms, including their gait impairments. However, proportion patients actually report benefits from experiencing—or even purposely inducing—stressful high-arousal situations. Using data large-scale international survey study among 4324 PD and impairments within the online Fox Insight (USA) ParkinsonNEXT (NL) cohorts, we demonstrate that individuals deploy an array mental state alteration strategies to cope impairment. Crucially, these differ along axis arousal—some act heighten, whereas others diminish, overall sympathetic tone. Together, our observations suggest arousal may as double-edged sword for control in PD. We propose theoretical, neurobiological framework explain why heightened can have detrimental effects on occurrence severity some individuals, while alleviating them others. Specifically, postulate this seemingly contradictory phenomenon is explained by inherent features ascending system: namely, related task performance inverted u-shaped curve (the so-called Yerkes Dodson relationship). noradrenergic locus coeruleus plays important role modulating symptom expression, regulating mediating network-level functional integration across brain. The ability facilitate dynamic ‘cross-talk’ between distinct, otherwise largely segregated brain regions necessary cerebral compensation presence suboptimal arousal, compensatory networks be too allow adequate compensation. Conversely, supraoptimal increased cross-talk competing inputs complementary emerge become dysfunctional. Because degenerates progression, finetuning delicate balance becomes increasingly difficult, heightening need self-modulate shifting sub- improve performance. Recognition underlying mechanism emphasises importance PD-specific rehabilitation alleviate disability.

Language: Английский

Citations

13
Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions DOI Creative Commons
Dániel Veréb, Mite Mijalkov, Anna Canal‐Garcia

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 9, 2023

The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown the LC heterogeneous connections cellular features, no yet assessed functional topography vivo, how this heterogeneity changes over aging, whether it associated with cognition mood. Here, we employ gradient-based approach to characterize organization aging using 3T resting-state fMRI population-based cohort aged from 18 88 years age (Cambridge Centre for Ageing Neuroscience cohort, n=618). We show exhibits rostro-caudal gradient along longitudinal axis, which was replicated independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). main direction consistent across groups, spatial features varied increasing age, emotional memory, emotion regulation. More specifically, loss rostral-like connectivity, more clustered topography, greater asymmetry between right left gradients higher worse behavioral performance. Furthermore, participants higher-than-normal Hospital Anxiety Depression Scale (HADS) ratings exhibited alterations as well, manifested asymmetry. These results provide vivo account imply are relevant markers LC-related measures psychopathology.

Language: Английский

Citations

13
Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson’s Disease DOI Creative Commons
Hendrik Theis, Nicola Pavese, Irena Rektorová

et al.

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(s2), P. S353 - S365

Published: Feb. 6, 2024

Assessing imaging biomarker in the prodromal and early phases of Parkinson’s disease (PD) is great importance to ensure an safe diagnosis. In last decades, modalities advanced are now able assess many different aspects neurodegeneration PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT with Ioflupane, more specific PET tracers degeneration dopaminergic system available. Furthermore, metabolic patterns be used anticipate a phenoconversion PD manifest this regard, it worth mentioning that inflammation will gain significance. Molecular neurotransmitters like serotonin, noradrenaline acetylcholine shed light on non-motor symptoms. Outside brain, molecular heart gut PD-related autonomous nervous system. Moreover, optical coherence tomography noninvasively detect retinal fibers as potential review, we describe these state-of-the-art point out how far techniques future pave way towards biomarker-based staging

Language: Английский

Citations

5
Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy DOI Creative Commons
Alexandre Berger, Elise Beckers, Vincent Joris

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 13, 2024

The locus coeruleus–norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This known prevent seizure development and induce long-term plastic changes, particularly with release norepinephrine hippocampus. However, requisites become responder therapy mechanisms action are still under investigation. Using MRI, we assessed structural functional characteristics coeruleus microstructural properties coeruleus-hippocampus white matter tracts patients drug-resistant epilepsy responding or not therapy. Twenty-three epileptic cervical stimulation were recruited for this pilot study, including 13 responders partial 10 non-responders. A dedicated MRI acquisition allowed vivo localization computation its contrast (an accepted marker LC integrity). Locus activity was estimated using during an auditory oddball task. Finally, multi-shell diffusion used estimate tracts. These compared between responders/partial non-responders their association duration also explored. In a better response therapy, trends toward lower higher found left medial right caudal portions coeruleus, respectively. An increased contrast, bilaterally over portions, correlated treatment. integrity connections new insights into neurobiology may provide novel markers treatment reflect neuroplasticity occurring brain following implantation.

Language: Английский

Citations

5
Noradrenergic neuromodulation in ageing and disease DOI Creative Commons

Friedrich Krohn,

Elisa Lancini, Mareike Ludwig

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105311 - 105311

Published: July 10, 2023

The locus coeruleus (LC) is a small brainstem structure located in the lower pons and main source of noradrenaline (NA) brain. Via its phasic tonic firing, it modulates cognition autonomic functions involved brain's immune response. extent degeneration to LC healthy ageing remains unclear, however, noradrenergic dysfunction may contribute pathogenesis Alzheimer's (AD) Parkinson's disease (PD). Despite their differences progression at later stages, early involvement lead comparable behavioural symptoms such as preclinical sleep problems neuropsychiatric result AD PD pathology. In this review, we draw attention mechanisms that underlie ageing, PD. We aim motivate future research investigate how system play pivotal role which also be relevant other neurodegenerative diseases.

Language: Английский

Citations

12