The Contribution of the Locus Coeruleus–Noradrenaline System Degeneration during the Progression of Alzheimer’s Disease

Mercan, Dilek; Heneka, Michael T.

doi:10.3390/biology11121822

Cited by 13 publications

(11 citation statements)

References 214 publications

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“…In fact, recent evidence suggests that an axon terminal damage of the LC-NE system is reminiscent of limbic degeneration, which occurs during early Alzheimer’s disease (AD) and PD and provides potential mechanisms underlying prodromal neuropsychiatric symptoms, which are grounded on the accumulation of deleterious proteins [ 111 ]. Based on such a strong background assessing severe damage to LC in the course of degenerative dementia and limbic involvement in PD, experimental studies in mammals and brain imaging techniques allow us to establish in vivo in humans a tight time course between LC degeneration and the occurrence of degenerative dementia [ 112 , 113 , 114 , 115 , 116 ]. The protective effects of LC-NE innervation are either worsened or improved by damage to LC neurons or a stimulation of NE receptors, respectively [ 110 , 117 , 118 , 119 ].…”

Section: Discussionmentioning

confidence: 99%

Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

Biagioni,

Ferrucci,

Lazzeri

et al. 2024

IJMS

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The present investigation was designed based on the evidence that, in neurodegenerative disorders, such as Alzheimer’s dementia (AD) and Parkinson’s disease (PD), damage to the locus coeruleus (LC) arising norepinephrine (NE) axons (LC-NE) is documented and hypothesized to foster the onset and progression of neurodegeneration within target regions. Specifically, the present experiments were designed to assess whether selective damage to LC-NE axons may alter key proteins involved in neurodegeneration within specific limbic regions, such as the hippocampus and piriform cortex, compared with the dorsal striatum. To achieve this, a loss of LC-NE axons was induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) in C57 Black mice, as assessed by a loss of NE and dopamine-beta-hydroxylase within target regions. In these experimental conditions, the amount of alpha-synuclein (alpha-syn) protein levels were increased along with alpha-syn expressing neurons within the hippocampus and piriform cortex. Similar findings were obtained concerning phospho-Tau immunoblotting. In contrast, a decrease in inducible HSP70-expressing neurons and a loss of sequestosome (p62)-expressing cells, along with a loss of these proteins at immunoblotting, were reported. The present data provide further evidence to understand why a loss of LC-NE axons may foster limbic neurodegeneration in AD and limbic engagement during PD.

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Section: Discussionmentioning

confidence: 99%

Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

Biagioni,

Ferrucci,

Lazzeri

et al. 2024

IJMS

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“…However, the consequences of such differences for neuromodulation remain unknown and await clarification. Finally, both the noradrenergic system and astrocytes are involved in the etiology of CNS disorders such as epilepsy (Ghasemi and Mehranfard, 2018;Vezzani et al, 2022) and Alzheimer's disease (Leanza et al, 2018;Mercan and Heneka, 2022;Perez, 2023). Our work might, therefore, open up new therapeutic avenues, establishing astrocytes as valid alternative targets for therapeutics targeting the NA system.…”

Section: Discussionmentioning

confidence: 99%

The astrocyte α1-adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex

Wahis

Akkaya

Kirunda

et al. 2023

Preprint

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Noradrenaline (norepinephrine) is known to modulate many physiological functions and behaviors. In this study, we tested to what extent astrocytes, a type of glial cell, participate in noradrenergic signaling in mouse primary visual cortex (V1). Astrocytes are essential partners of neurons in the central nervous system. They are central to brain homeostasis, but also dynamically regulate neuronal activity, notably by relaying and regulating neuromodulator signaling. Indeed, astrocytes express receptors for multiple neuromodulators, including noradrenaline, but the extent to which astrocytes are involved in noradrenergic signaling remains unclear. To test whether astrocytes are involved in noradrenergic neuromodulation in mice, we knocked down the major noradrenaline receptor in astrocytes, the alpha 1A-adrenoreceptor. Using this model, we found that the alpha 1A-adrenoreceptor is involved in triggering intracellular calcium transients in astrocytes, which are generally thought to underlie astrocyte function. To test if impaired alpha 1A-adrenoreceptor signaling in astrocytes affected the function of neuronal circuits in V1, we used electrophysiological measurements and found that noradrenergic signaling through astrocyte alpha 1A-adrenoreceptor controls the basal level of inhibition and regulates plasticity in V1 by potentiating synaptic responses in circuits involved in visual information processing.

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“…The second aspect may concern the field of rehabilitation. There is growing evidence that neurodegenerative diseases may be triggered by neurodegenerative processes occurring in the LC [ 73 , 74 ]. In parallel, it is well known that a masticatory deficit may lead to brain neurodegenerative processes [ 18 , 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

Trigeminal Stimulation and Visuospatial Performance: The Struggle between Chewing and Trigeminal Asymmetries

Tramonti Fantozzi,

De Cicco,

d’Ascanio

et al. 2023

Biomedicines

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Chewing improves visuospatial performance through locus coeruleus (LC) activation. The effects of bilateral and unilateral mastication were investigated in subjects showing different degrees of asymmetry in masseter electromyographic (EMG) activity during clenching and in pupil size at rest (anisocoria), which is a proxy of LC imbalance. Correlations between performance changes and asymmetry values were found in males, but not in females. Among males, subjects with low asymmetry values (balanced-BAL) were more sensitive than those with high asymmetry values (imbalanced-IMB) to bilateral and unilateral chewing on the side with higher EMG activity (hypertonic). The opposite was true for hypotonic side chewing. BAL subjects were sensitive to unilateral chewing on both sides, while in IMB subjects, hypertonic side chewing did not influence performance in either males or females. Bilateral chewing elicited larger effects in BAL subjects than in IMB subjects, exceeding the values predicted from unilateral chewing in both groups. Finally, pupil size and anisocoria changes elicited by chewing were correlated with asymmetry values, independent of sex. Data confirmed the facilitation of visuospatial performance exerted by chewing. Trigeminal asymmetries modulate the chewing effects, making occlusal rebalancing an appropriate strategy to improve performance.

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The Contribution of the Locus Coeruleus–Noradrenaline System Degeneration during the Progression of Alzheimer’s Disease

Cited by 13 publications

References 214 publications

Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

The astrocyte α1-adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex

Trigeminal Stimulation and Visuospatial Performance: The Struggle between Chewing and Trigeminal Asymmetries

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