Locus Coeruleus and neurovascular unit: From its role in physiology to its potential role in Alzheimer’s disease pathogenesis

Giorgi, Filippo Sean; Galgani, Alessandro; Puglisi-Allegra, Stefano; Limanaqi, Fiona; Busceti, Carla Letizia

doi:10.1002/jnr.24718

Cited by 42 publications

(46 citation statements)

References 231 publications

(441 reference statements)

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“…• fundamental role in coupling the energy demand of activated brain regions with regional cerebral blood flow • includes the BBB • active role in neuroinflammation • participates to the glymphatic system Giorgi et al, (2020) F I G U R E 1 Electron micrograph showing the components of the NVU and the intimate connections between them: A -astrocyte, BM -basement membrane, EC -endothelial cell, L -lumen, Nneuron, P -pericyte, Syn -synapse molecules, which can induce transcriptional changes in BEC and further impact the structure and function of the brain, increasing the likelihood of neurodegenerative disease (Chen et al, 2020). Additionally, the BBB multidrug resistance decreases with ageing in a region-specific manner, eventually leading to a poor clearance of neurotoxic compounds and accumulation of oxidative stress products, this too promoting neurodegenerative disease (Whitton, 2007).…”

Section: Definitionmentioning

confidence: 99%

CD36 – A novel molecular target in the neurovascular unit

Ioghen

Chițoiu

Gherghiceanu

et al. 2021

Eur J of Neuroscience

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CD36 is an integral membrane protein primarily known for its function as a fatty acid transporter, yet also playing other biological roles from lipid metabolism to inflammation modulation. These pleiotropic effects are explained by the existence of multiple different ligands and the extensive distribution in numerous cell types. Moreover, the receptor is related to various pathologies and it may prove to be a good target for prospective therapeutic strategies. In the neurovascular unit (NVU), CD36 is expressed in cells like microglia, microvascular endothelial cells, astrocytes and neurons. In the normal brain, CD36 was proven to be involved in phagocytosis of apoptotic cells, oro‐sensory detection of dietary lipids, and fatty acid transport across the blood brain barrier (BBB). CD36 was also acknowledged as a potentially important player in central nervous system (CNS) disorders, such as Alzheimer Disease‐associated vascular dysfunction and oxidative stress and the neuroinflammatory response in stroke. Despite continuous efforts, the therapeutic arsenal for such diseases is still scarce and there is an increasing interest in discovering new molecular targets for more specific therapeutic approaches. In this review, we summarize the role of CD36 in the normal function of the NVU and in several CNS disorders, focusing on the dysregulation of the NVU and the potential therapeutic modulation.

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Section: Definitionmentioning

confidence: 99%

CD36 – A novel molecular target in the neurovascular unit

Ioghen

Chițoiu

Gherghiceanu

et al. 2021

Eur J of Neuroscience

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“…When brain activity in a certain area of the brain increases, the oxygen demand increases in that area, which will make more HbR combined with oxygen molecules become HbO to increase oxygen transport. Conversely, when brain activity in that area decreases, the amount of HbO decreases [ 33 , 34 ]. That is the HR.…”

Section: Resultsmentioning

confidence: 99%

Decoding of Walking Imagery and Idle State Using Sparse Representation Based on fNIRS

Gong

Lei

et al. 2021

Computational Intelligence and Neuroscience

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Objectives. Brain-computer interface (BCI) based on functional near-infrared spectroscopy (fNIRS) is expected to provide an optional active rehabilitation training method for patients with walking dysfunction, which will affect their quality of life seriously. Sparse representation classification (SRC) oxyhemoglobin (HbO) concentration was used to decode walking imagery and idle state to construct fNIRS-BCI based on walking imagery. Methods. 15 subjects were recruited and fNIRS signals were collected during walking imagery and idle state. Firstly, band-pass filtering and baseline drift correction for HbO signal were carried out, and then the mean value, peak value, and root mean square (RMS) of HbO and their combinations were extracted as classification features; SRC was used to identify the extracted features and the result of SRC was compared with those of support vector machine (SVM), K-Nearest Neighbor (KNN), linear discriminant analysis (LDA), and logistic regression (LR). Results. The experimental results showed that the average classification accuracy for walking imagery and idle state by SRC using three features combination was 91.55 ± 3.30%, which was significantly higher than those of SVM, KNN, LDA, and LR (86.37 ± 4.42%, 85.65 ± 5.01%, 86.43 ± 4.41%, and 76.14 ± 5.32%, respectively), and the classification accuracy of other combined features was higher than that of single feature. Conclusions. The study showed that introducing SRC into fNIRS-BCI can effectively identify walking imagery and idle state. It also showed that different time windows for feature extraction have an impact on the classification results, and the time window of 2–8 s achieved a better classification accuracy (94.33 ± 2.60%) than other time windows. Significance. The study was expected to provide a new and optional active rehabilitation training method for patients with walking dysfunction. In addition, the experiment was also a rare study based on fNIRS-BCI using SRC to decode walking imagery and idle state.

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“…The impairment of LC may bear other detrimental effects in AD pathogenesis, besides its role in tau pathology spreading. In fact, LC-NA system plays an important neuroprotective role in physiological conditions, regulating microglia activity and modulating neurovascular unit functioning (Giorgi et al 2020a;Heneka et al 2015).…”

Section: The Loss Of Neuroprotective Effects Of Lc Efferences May Enhance Ad Pathology Also In the Hypothalamusmentioning

confidence: 99%

“…The experimental lesion of LC by DSP-4 in mice models causes an increase in pro-inflammatory cytokines secretion (Feinstein et al 2002;Heneka et al 2003) and aberrant activation of microglial cells (Heneka et al 2010;Jardanhazi-Kurutz et al 2011), which is associated with a reduced efficacy in amyloid phagocytosis and clearance in AD models (Heneka et al 2006). Moreover, LC exerts an important role in the function of neurovascular unit, both by regulating cerebral blood flow and by modulating the activity of the blood-brain barrier (BBB) (Giorgi et al 2020a). LC lesion induces the disruption of BBB and cerebral blood flow imbalance, thus causing a condition of relative hypoxia; both phenomena contribute to neurodegenerative processes, by promoting neuroinflammation, worsening cellular damage and abnormal protein accumulation (Kalinin et al 2006;Zlokovic 2011;Bekar et al 2012;de la Torre 2017;Giorgi et al 2020a;Yu et al 2020).…”

Section: The Loss Of Neuroprotective Effects Of Lc Efferences May Enhance Ad Pathology Also In the Hypothalamusmentioning

confidence: 99%

“…The noradrenergic nucleus Locus Coeruleus (LC) is the main noradrenergic (NA) nucleus of the brain, providing NA innervation for the whole cortical mantle and many subcortical structures (Poe et al 2020). LC-NA system significantly contributes to several brain functions; it promotes brain homeostasis, modulating neurovascular unit functioning and neuronal-glial interaction, it takes part in a variety of cognitive processes, ranging from focused attention to learning and memory formation, and it plays a crucial role in modulating the sleep-waking cycle (Aston-Jones and Cohen 2005; Lecrux and Hamel 2016;Foote and Berridge 2019;Giorgi et al 2020a). LC has been receiving growing attention in the last years for its possible pathogenic and pathophysiological role in AD (Giorgi et al 2017;Kelly et al 2017), since it may be markedly involved since the earliest stages of the disease .…”

Section: Introductionmentioning

confidence: 99%

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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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Locus Coeruleus and neurovascular unit: From its role in physiology to its potential role in Alzheimer’s disease pathogenesis

Cited by 42 publications

References 231 publications

CD36 – A novel molecular target in the neurovascular unit

CD36 – A novel molecular target in the neurovascular unit

Decoding of Walking Imagery and Idle State Using Sparse Representation Based on fNIRS

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

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