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Article ; Online: Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging.

Giunta, Sergio / Giordani, Chiara / De Luca, Maria / Olivieri, Fabiola

2024 Volume 218, Page(s) 111915

Abstract: The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most ... ...

Abstract	The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most common age-related diseases. These conditions are linked to the presence of symptoms of autonomic dysfunction, in association with low cortisol levels, suggestive of reduced hypothalamic-pituitary-adrenal (HPA) axis activity, and with increased pro-inflammatory condition. Alterations of dopamine and serotonin neurotransmitter levels were also recently observed in LC. Interestingly, at least some of the proposed mechanisms of LC development overlap with mechanisms of Autonomic Nervous System (ANS) imbalance, previously detailed in the framework of the aging process. ANS imbalance is characterized by a proinflammatory sympathetic overdrive, and a concomitant decreased anti-inflammatory vagal parasympathetic activity, associated with reduced anti-inflammatory effects of the HPA axis and cholinergic anti-inflammatory pathway (CAP). These neuro-immune-endocrine system imbalanced activities fuel the vicious circle of chronic inflammation, i.e. inflammaging. Here, we refine our original hypothesis that ANS dysfunction fuels inflammaging and propose that biomarkers of ANS imbalance could also be considered biomarkers of inflammaging, recognized as the main risk factor for developing age-related diseases and the sequelae of viral infections, i.e. LC.
MeSH term(s)	Humans ; Post-Acute COVID-19 Syndrome ; Hypothalamo-Hypophyseal System/physiology ; Quality of Life ; Pituitary-Adrenal System/physiology ; COVID-19 ; Chronic Disease ; Biomarkers ; Anti-Inflammatory Agents
Chemical Substances	Biomarkers ; Anti-Inflammatory Agents
Language	English
Publishing date	2024-02-13
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	183915-9
ISSN	1872-6216 ; 0047-6374
ISSN (online)	1872-6216
ISSN	0047-6374
DOI	10.1016/j.mad.2024.111915
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Article ; Online: THC and CBD: Villain versus Hero? Insights into Adolescent Exposure.

Pintori, Nicholas / Caria, Francesca / De Luca, Maria Antonietta / Miliano, Cristina

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Cannabis is the most used drug of abuse worldwide. It is well established that the most abundant phytocannabinoids in this plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet ... ...

Abstract	Cannabis is the most used drug of abuse worldwide. It is well established that the most abundant phytocannabinoids in this plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet vastly different effects in the brain. By binding to the same receptors, THC is psychoactive, while CBD has anxiolytic and antipsychotic properties. Lately, a variety of hemp-based products, including CBD and THC, have become widely available in the food and health industry, and medical and recreational use of cannabis has been legalized in many states/countries. As a result, people, including youths, are consuming CBD because it is considered "safe". An extensive literature exists evaluating the harmful effects of THC in both adults and adolescents, but little is known about the long-term effects of CBD exposure, especially in adolescence. The aim of this review is to collect preclinical and clinical evidence about the effects of cannabidiol.
MeSH term(s)	Adult ; Adolescent ; Humans ; Cannabidiol/pharmacology ; Dronabinol/adverse effects ; Cannabis/chemistry ; Cannabinoid Receptor Agonists ; Anti-Anxiety Agents ; Hallucinogens
Chemical Substances	Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S) ; Cannabinoid Receptor Agonists ; Anti-Anxiety Agents ; Hallucinogens
Language	English
Publishing date	2023-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065251
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Article ; Online: Serum syndecan-4 correlates with blood pressure and cardiovascular parameters but not proinflammatory markers in healthy older women.

De Luca, Maria / Bryan, David Ronald / Hunter, Gary Richard

Aging clinical and experimental research

2022 Volume 34, Issue 10, Page(s) 2541–2545

Abstract: Aging is accompanied by a low-grade proinflammatory status that plays a role in age-related vascular alterations. Syndecan-4 (SDC4) is a key component of the endothelial glycocalyx, and its extracellular domain can be shed by matrix metalloproteinase-9 ( ... ...

Abstract	Aging is accompanied by a low-grade proinflammatory status that plays a role in age-related vascular alterations. Syndecan-4 (SDC4) is a key component of the endothelial glycocalyx, and its extracellular domain can be shed by matrix metalloproteinase-9 (MMP-9). In vitro studies demonstrated that MMP-9-mediated shedding of SDC4 is induced by tumor necrosis factor-α (TNF- α) in human endothelial cells. However, the relationship between circulating shed SDC4, systemic inflammation, and age-related vascular alterations remains unknown. Here, we used linear regression models to examine the associations of serum SDC4 levels with cardiovascular hemodynamic phenotypes, serum MMP-9, and serum TNF-α and inteleukin-6 in healthy older women (n = 74). Serum SDC4 was not associated with proinflammatory cytokines or arterial elasticity. Nevertheless, we found significant correlations of SDC4 with MMP-9, heart rate, left ventricular ejection time, systemic vascular resistance, and blood pressure. Our preliminary evidence suggests that systemic inflammation might not induce SDC4 shedding in healthy aging.
MeSH term(s)	Aged ; Female ; Humans ; Blood Pressure ; Endothelial Cells ; Inflammation ; Matrix Metalloproteinase 9/blood ; Syndecan-4/blood ; Tumor Necrosis Factor-alpha/blood ; Cardiovascular Physiological Phenomena ; Heart Rate ; Ventricular Function, Left
Chemical Substances	Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Syndecan-4 ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-08-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2104785-6
ISSN	1720-8319 ; 1594-0667
ISSN (online)	1720-8319
ISSN	1594-0667
DOI	10.1007/s40520-022-02210-z
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Zs.A 3343: Show issues

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Article ; Online: The role of the cell-matrix interface in aging and its interaction with the renin-angiotensin system in the aged vasculature.

De Luca, Maria

Mechanisms of ageing and development

2018 Volume 177, Page(s) 66–73

Abstract: The extracellular matrix (ECM) is an intricate network that provides structural and anchoring support to cells in order to stabilize cell morphology and tissue architecture. The ECM also controls many aspects of the cell's dynamic behavior and fate ... ...

Abstract	The extracellular matrix (ECM) is an intricate network that provides structural and anchoring support to cells in order to stabilize cell morphology and tissue architecture. The ECM also controls many aspects of the cell's dynamic behavior and fate through its ongoing, bidirectional interaction with cells. These interactions between the cell and components of the surrounding ECM are implicated in several biological processes, including development and adult tissue repair in response to injury, throughout the lifespan of multiple species. The present review gives an overview of the growing evidence that cell-matrix interactions play a pivotal role in the aging process. The focus of the first part of the article is on recent studies using cell-derived decellularized ECM, which strongly suggest that age-related changes in the ECM induce cellular senescence, a well-recognized hallmark of aging. This is followed by a review of findings from genetic studies indicating that changes in genes involved in cell-ECM adhesion and matrix-mediated intracellular signaling cascades affect longevity. Finally, mention is made of novel data proposing an intricate interplay between cell-matrix interactions and the renin-angiotensin system that may have a significant impact on mammalian arterial stiffness with age.
MeSH term(s)	Aging/metabolism ; Aging/pathology ; Animals ; Arteries/metabolism ; Arteries/pathology ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Humans ; Renin-Angiotensin System ; Vascular Stiffness
Language	English
Publishing date	2018-04-04
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	183915-9
ISSN	1872-6216 ; 0047-6374
ISSN (online)	1872-6216
ISSN	0047-6374
DOI	10.1016/j.mad.2018.04.002
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Zs.A 1012: Show issues

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Article ; Online: Role of the V1G1 subunit of V-ATPase in breast cancer cell migration.

De Luca, Maria / Romano, Roberta / Bucci, Cecilia

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4615

Abstract: V-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the ... ...

Abstract	V-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.
MeSH term(s)	Breast Neoplasms/enzymology ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement ; Female ; Humans ; Lysosomes/metabolism ; Microscopy, Fluorescence ; Neoplasm Invasiveness ; Real-Time Polymerase Chain Reaction ; Vacuolar Proton-Translocating ATPases/metabolism ; Vacuolar Proton-Translocating ATPases/physiology ; rab7 GTP-Binding Proteins/metabolism ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	RAC1 protein, human ; rab7 GTP-Binding Proteins ; rab7 GTP-binding proteins, human ; ATP6V1G1 protein, human (EC 3.6.1.-) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2021-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-84222-9
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Article: Interpreting Developmental Surface Dyslexia within a Comorbidity Perspective.

Zoccolotti, Pierluigi / De Luca, Maria / Marinelli, Chiara Valeria

Brain sciences

2021 Volume 11, Issue 12

Abstract: Recent evidence underlines the importance of seeing learning disorders in terms of their partial association (comorbidity). The present concept paper presents a model of reading that aims to account for performance on a naturalistic reading task within a ...

Abstract	Recent evidence underlines the importance of seeing learning disorders in terms of their partial association (comorbidity). The present concept paper presents a model of reading that aims to account for performance on a naturalistic reading task within a comorbidity perspective. The model capitalizes on the distinction between three independent levels of analysis: competence, performance, and acquisition: Competence denotes the ability to master orthographic-phonological binding skills;
Language	English
Publishing date	2021-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci11121568
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Article ; Online: Circulating Levels of the Heparan Sulfate Proteoglycan Syndecan-4 Positively Associate with Blood Pressure in Healthy Premenopausal Women.

De Luca, Maria / Bryan, David R / Hunter, Gary R

Biomolecules

2021 Volume 11, Issue 3

Abstract: Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell-matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 ... ...

Abstract	Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell-matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 and SDC4 are associated with hypertension and cardiovascular diseases, but their relationships with cardiovascular risk factors in healthy individuals are unknown. The primary objective of this study was to investigate whether serum levels of SDC4 and SDC1 were associated with body composition, hemodynamic parameters, pro-inflammatory cytokine concentrations, and urinary noradrenaline and dopamine levels in healthy women (17 African American and 20 European American) between the ages of 20 and 40 years old. Univariate analyses revealed only a significant (
MeSH term(s)	Adult ; Body Composition/physiology ; Catecholamines/blood ; Dopamine/blood ; Female ; Heparan Sulfate Proteoglycans/blood ; Humans ; Hypertension/blood ; Norepinephrine/blood ; Premenopause ; Syndecan-4/blood ; Young Adult
Chemical Substances	Catecholamines ; Heparan Sulfate Proteoglycans ; SDC4 protein, human ; Syndecan-4 ; Dopamine (VTD58H1Z2X) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2021-02-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11030342
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Article ; Online: The potential role of oxytocin in addiction: What is the target process?

Sanna, Fabrizio / De Luca, Maria Antonietta

Current opinion in pharmacology

2021 Volume 58, Page(s) 8–20

Abstract: Oxytocin regulates a variety of centrally-mediated functions, ranging from socio-sexual behavior, maternal care, and affiliation to fear, stress, anxiety. In the past years, both clinical and preclinical studies characterized oxytocin for its modulatory ... ...

Abstract	Oxytocin regulates a variety of centrally-mediated functions, ranging from socio-sexual behavior, maternal care, and affiliation to fear, stress, anxiety. In the past years, both clinical and preclinical studies characterized oxytocin for its modulatory role on reward-related neural substrates mainly involving the interplay with the mesolimbic and mesocortical dopaminergic pathways. This suggests a role of this nonapeptide on the neurobiology of addiction raising the possibility of its therapeutic use. Although far from a precise knowledge of the underlying mechanisms, the putative role of the bed nucleus of the stria terminalis as a key structure where oxytocin may rebalance altered neurochemical processes and neuroplasticity involved in dependence and relapse has been highlighted. This view opens new opportunities to address the health problems related to drug misuse.
MeSH term(s)	Anxiety ; Humans ; Neuronal Plasticity ; Oxytocin ; Septal Nuclei
Chemical Substances	Oxytocin (50-56-6)
Language	English
Publishing date	2021-04-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2021.03.002
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Zs.A 5608: Show issues

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Article ; Online: Immune and glial cell alterations in the rat brain after repeated exposure to the synthetic cannabinoid JWH-018.

Pintori, Nicholas / Mostallino, Rafaela / Spano, Enrica / Orrù, Valeria / Piras, Maria Grazia / Castelli, Maria Paola / De Luca, Maria Antonietta

Journal of neuroimmunology

2024 Volume 389, Page(s) 578325

Abstract: The use of synthetic cannabinoid receptor agonists (SCRAs) poses major psychiatric risks. We previously showed that repeated exposure to the prototypical SCRA JWH-018 induces alterations in dopamine (DA) transmission, abnormalities in the emotional state, ...

Abstract	The use of synthetic cannabinoid receptor agonists (SCRAs) poses major psychiatric risks. We previously showed that repeated exposure to the prototypical SCRA JWH-018 induces alterations in dopamine (DA) transmission, abnormalities in the emotional state, and glial cell activation in the mesocorticolimbic DA circuits of rats. Despite growing evidence suggesting the relationship between substance use disorders (SUD) and neuroinflammation, little is known about the impact of SCRAs on the neuroimmune system. Here, we investigated whether repeated JWH-018 exposure altered neuroimmune signaling, which could be linked with previously reported central effects. Adult male Sprague-Dawley (SD) rats were exposed to JWH-018 (0.25 mg/kg, i.p.) for fourteen consecutive days, and the expression of cytokines, chemokines, and growth factors was measured seven days after treatment discontinuation in the striatum, cortex, and hippocampus. Moreover, microglial (ionized calcium-binding adaptor molecule 1, IBA-1) and astrocyte (glial fibrillary acidic protein, GFAP) activation markers were evaluated in the caudate-putamen (CPu). Repeated JWH-018 exposure induces a perturbation of neuroimmune signaling specifically in the striatum, as shown by increased levels of cytokines [interleukins (IL) -2, -4, -12p70, -13, interferon (IFN) γ], chemokines [macrophage inflammatory protein (MIP) -1α, -3α], and growth factors [macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF)], together with increased IBA-1 and GFAP expression in the CPu. JWH-018 exposure induces persistant brain region-specific immune alterations up to seven days after drug discontinuation, which may contribute to the behavioral and neurochemical dysregulations in striatal areas that play a role in the reward-related processes that are frequently impaired in SUD.
MeSH term(s)	Rats ; Male ; Animals ; Vascular Endothelial Growth Factor A ; Rats, Sprague-Dawley ; Cannabinoids/metabolism ; Cannabinoids/pharmacology ; Cannabinoids/therapeutic use ; Brain/metabolism ; Cytokines/metabolism ; Chemokines/metabolism ; Microglia/metabolism ; Dopamine/pharmacology ; Indoles ; Naphthalenes
Chemical Substances	1-pentyl-3-(1-naphthoyl)indole (G391998J57) ; Vascular Endothelial Growth Factor A ; Cannabinoids ; Cytokines ; Chemokines ; Dopamine (VTD58H1Z2X) ; Indoles ; Naphthalenes
Language	English
Publishing date	2024-02-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2024.578325
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Article ; Online: Editorial of special issue - Synthetic psychoactive substances and neurological diseases: Toxic and therapeutic effects.

Simola, Nicola / De Luca, Maria Antonietta

Experimental neurology

2021 Volume 347, Page(s) 113921

MeSH term(s)	Humans ; Methamphetamine/adverse effects ; Methamphetamine/therapeutic use ; N-Methyl-3,4-methylenedioxyamphetamine/adverse effects ; N-Methyl-3,4-methylenedioxyamphetamine/therapeutic use ; Nervous System Diseases/chemically induced ; Nervous System Diseases/drug therapy ; Psychotropic Drugs/adverse effects ; Psychotropic Drugs/therapeutic use ; Treatment Outcome
Chemical Substances	Psychotropic Drugs ; Methamphetamine (44RAL3456C) ; N-Methyl-3,4-methylenedioxyamphetamine (KE1SEN21RM)
Language	English
Publishing date	2021-11-10
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2021.113921
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