Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

Galgani, Alessandro; Lombardo, Francesco; Latta, Daniele Della; Mondaini, Nicola; Bonuccelli, Ubaldo; Fornai, Francesco; Giorgi, Filippo Sean

doi:10.1007/s11910-020-01087-7

Cited by 35 publications

(32 citation statements)

References 96 publications

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“…As sleep spindles serve as EEG hallmarks to distinguish light and deep sleep states in human 6 , monitoring the LC in human sleep could also shed light on these and other 9, 44 unique aspects of primate sleep. Finally, there is strong evidence that LC and sleep disruptions could be linked in post-traumatic stress disorders 45 , in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease 44, 46 and in insomnia 47 . Our findings highlight a need to further develop tools to monitor LC activity in human sleep as a possible neural target for the origin of these sleep disruptions.…”

Section: Discussionmentioning

confidence: 99%

Noradrenergic circuit control of non-REM sleep substates

Osorio-Forero

Cardis

Vantomme

et al. 2021

Preprint

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The continuity of non-rapid-eye-movement sleep (NREMS) is essential for its functions. However, many mammalian species, including humans, show NREMS fragility to maintain environmental vigilance. The neural substrates balancing NREMS continuity and fragility substates are unexplored. We show that the locus coeruleus (LC) is necessary and sufficient to generate infraslow (~50 s) continuity-fragility fluctuations in mouse NREMS. Through machine-learning-guided closed-loop optogenetic LC interrogation, we suppressed, locked, or entrained continuity-fragility fluctuations, as evident by LC-mediated regulation of sleep spindle clustering and heart rate variability. Noradrenergic modulation of thalamic but not cortical circuits was required for infraslow sleep spindle clustering and involved rapid noradrenaline increases that activated both α1- and β-adrenergic receptors to cause slowly decaying membrane depolarizations. The LC thus coordinates brain and bodily states during NREMS to engender continuity-fragility, accentuating its role in the physiology of sleep-related sensory uncoupling and as target in sleep disorders showing abnormal cortical and/or autonomic arousability.

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Section: Discussionmentioning

confidence: 99%

Noradrenergic circuit control of non-REM sleep substates

Osorio-Forero

Cardis

Vantomme

et al. 2021

Preprint

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“…Interestingly, promising LC neuroimaging biomarkers have also been developed recently, which for the first time may allow to evaluate human LC-hypothalamus pathology in vivo. Indeed, LC can be studied by MRI profiting of T1-weighted neuromelanin-sensitive sequences (Galgani et al 2020 ; Liu et al 2017 ), and this approach has already been applied to assess LC involvement in healthy elderly subjects (Liu et al 2020 ), as well as in patients affected by several neurological disorders, including AD, PD, REM-behavior disorder, Multiple system Atrophy, chronic traumatic encephalopathy essential tremor (e.g., García-Lorenzo et al 2013 ; Matsuura et al 2013 ; Isaias et al 2016 ; Betts et al 2019 ). Positron Emission Tomography tracers specific for NA terminal transporters are also under development, such as 11 C-MeNER, which has been tested already in PD patients (Sommerauer et al 2018 ; Doppler et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The connections of Locus Coeruleus with hypothalamus: potential involvement in Alzheimer’s disease

Giorgi

Galgani²,

Puglisi-Allegra

et al. 2021

J Neural Transm

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The hypothalamus and Locus Coeruleus (LC) share a variety of functions, as both of them take part in the regulation of the sleep/wake cycle and in the modulation of autonomic and homeostatic activities. Such a functional interplay takes place due to the dense and complex anatomical connections linking the two brain structures. In Alzheimer’s disease (AD), the occurrence of endocrine, autonomic and sleep disturbances have been associated with the disruption of the hypothalamic network; at the same time, in this disease, the occurrence of LC degeneration is receiving growing attention for the potential roles it may have both from a pathophysiological and pathogenetic point of view. In this review, we summarize the current knowledge on the anatomical and functional connections between the LC and hypothalamus, to better understand whether the impairment of the former may be responsible for the pathological involvement of the latter, and whether the disruption of their interplay may concur to the pathophysiology of AD. Although only a few papers specifically explored this topic, intriguingly, some pre-clinical and post-mortem human studies showed that aberrant protein spreading and neuroinflammation may cause hypothalamus degeneration and that these pathological features may be linked to LC impairment. Moreover, experimental studies in rodents showed that LC plays a relevant role in modulating the hypothalamic sleep/wake cycle regulation or neuroendocrine and systemic hormones; in line with this, the degeneration of LC itself may partly explain the occurrence of hypothalamic-related symptoms in AD.

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“…Neuronal loss may occur in the locus coeruleus at a very early stage of Alzheimer's disease progression [8 ▪▪ ], prior to the accumulation of amyloid plaques and onset of symptoms [9] (Fig. 2).…”

Section: Early Locus Coeruleus Degenerationmentioning

confidence: 99%

The role of the locus coeruleus/norepinephrine system in the pathogenesis of neurodegenerative disorders: An update

Malatt

Tagliati²

2022

Current Opinion in Neurology

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Purpose of reviewThe aim of this review was to provide an update on current and emerging knowledge of the neuropathological processes affecting the locus coeruleus/norepinephrine (LC/NE) system, their effect on Alzheimer's disease and Parkinson's disease symptomatology, including efforts to translate these notions into therapeutic actions targeting the noradrenergic system.Recent findingsOver the past 2 years, work from multiple groups has contributed to support an early role of locus coeruleus degeneration and/or hyperactivation in the neurodegenerative process, including a trigger of neuroinflammation. Imaging advances are allowing the quantification of locus coeruleus structural features in vivo, which is critical in the early stages of disease. Nonmotor and noncognitive symptoms, often secondary to the involvement of the LC/NE system, are becoming more important in the definition of these diseases and their treatment.SummaryThe diverse symptomatology of Parkinson's disease and Alzheimer's disease, which is not limited to cardinal motor and cognitive abnormalities, strongly suggests a multisystem neurodegenerative process. In this context, it is increasingly clear how the LC/NE system plays a key role in the initiation and maintenance of the neurodegenerative process.

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Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

Cited by 35 publications

References 96 publications

Noradrenergic circuit control of non-REM sleep substates

Noradrenergic circuit control of non-REM sleep substates

The connections of Locus Coeruleus with hypothalamus: potential involvement in Alzheimer’s disease

The role of the locus coeruleus/norepinephrine system in the pathogenesis of neurodegenerative disorders: An update

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