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Article ; Online: Ascorbate and its transporter SVCT2: The dynamic duo's integrated roles in CNS neurobiology and pathophysiology.

Portugal, Camila C

2024 Volume 212, Page(s) 448–462

Abstract: Ascorbate is a small antioxidant molecule essential for the proper development and function of the brain. Ascorbate is transported into the brain and between brain cells via the Sodium vitamin C co-transporter 2 (SVCT2). This review provides an in-depth ... ...

Abstract	Ascorbate is a small antioxidant molecule essential for the proper development and function of the brain. Ascorbate is transported into the brain and between brain cells via the Sodium vitamin C co-transporter 2 (SVCT2). This review provides an in-depth analysis of ascorbate's physiology, including how ascorbate is absorbed from food into the CNS, emphasizing cellular mechanisms of ascorbate recycling and release in different CNS compartments. Additionally, the review delves into the various functions of ascorbate in the CNS, including its impact on epigenetic modulation, synaptic plasticity, and neurotransmission. It also emphasizes ascorbate's role on neuromodulation and its involvement in neurodevelopmental processes and disorders. Furthermore, it analyzes the relationship between the duo ascorbate/SVCT2 in neuroinflammation, particularly its effects on microglial activation, cytokine release, and oxidative stress responses, highlighting its association with neurodegenerative diseases, such as Alzheimer's disease (AD). Overall, this review emphasizes the crucial role of the dynamic duo ascorbate/SVCT2 in CNS physiology and pathology and the need for further research to fully comprehend its significance in a neurobiological context and its potential therapeutic applications.
MeSH term(s)	Ascorbic Acid ; Sodium-Coupled Vitamin C Transporters/genetics ; Neurobiology ; Antioxidants ; Symporters ; Vitamins
Chemical Substances	Ascorbic Acid (PQ6CK8PD0R) ; Sodium-Coupled Vitamin C Transporters ; Antioxidants ; Symporters ; Vitamins
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2023.12.040
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases

Portugal, Camila C. / Almeida, Tiago O. / Socodato, Renato / Relvas, João B.

The FEBS Journal. 2022 Dec., v. 289, no. 24 p.7760-7775

2022

Abstract: c‐Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the concept of Src family ... ...

Abstract	c‐Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the concept of Src family kinases (SFKs). Microglia are the resident innate immune cell population of the CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling the neuronal parenchyma and exerting neuroprotective actions. Activation of pathogen‐associated molecular pattern (PAMP) and damage‐associated molecular pattern (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, and changes in gene expression, concurrent with the secretion of cytokines, chemokines, and growth factors. A significant body of literature shows that SFK stimulation positively associates with microglial activation and neuropathological conditions, including Alzheimer's and Parkinson's diseases. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, and secretion of inflammatory mediators. In addition, we discuss the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases.
Keywords	Alzheimer disease ; brain ; chemokines ; homeostasis ; neurodegenerative diseases ; neuroglia ; parenchyma (animal tissue) ; pathogen-associated molecular patterns ; phagocytosis ; protein kinases ; secretion ; tyrosine
Language	English
Dates of publication	2022-12
Size	p. 7760-7775.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16197
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases.

Portugal, Camila C / Almeida, Tiago O / Socodato, Renato / Relvas, João B

The FEBS journal

2021

Abstract: c-Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine-phosphorylating protein kinases with a similar structure to c-Src gave rise to the concept of Src family ... ...

Abstract	c-Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine-phosphorylating protein kinases with a similar structure to c-Src gave rise to the concept of Src family kinases (SFKs). Microglia are the resident innate immune cell population of the CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling the neuronal parenchyma and exerting neuroprotective actions. Activation of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, and changes in gene expression, concurrent with the secretion of cytokines, chemokines, and growth factors. A significant body of literature shows that SFK stimulation positively associates with microglial activation and neuropathological conditions, including Alzheimer's and Parkinson's diseases. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, and secretion of inflammatory mediators. In addition, we discuss the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases.
Language	English
Publishing date	2021-09-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16197
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: RhoA balances microglial reactivity and survival during neuroinflammation.

Socodato, Renato / Rodrigues-Santos, Artur / Tedim-Moreira, Joana / Almeida, Tiago O / Canedo, Teresa / Portugal, Camila C / Relvas, João B

Cell death & disease

2023 Volume 14, Issue 10, Page(s) 690

Abstract: Microglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia ... ...

Abstract	Microglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia inflammatory reactivity can lead to brain damage. Dynamic cytoskeleton reorganization correlates with alterations of microglial reactivity driven by external cues, and proteins controlling cytoskeletal reorganization, such as the Rho GTPase RhoA, are well positioned to refine or adjust the functional state of the microglia during injury, disease, or inflammation. Here, we use multi-biosensor-based live-cell imaging approaches and tissue-specific conditional gene ablation in mice to understand the role of RhoA in microglial response to inflammation. We found that a decrease in RhoA activity is an absolute requirement for microglial metabolic reprogramming and reactivity to inflammation. However, without RhoA, inflammation disrupts Ca
MeSH term(s)	Mice ; Animals ; Microglia/metabolism ; Neuroinflammatory Diseases ; Inflammation/metabolism ; Necrosis/metabolism ; Apoptosis
Language	English
Publishing date	2023-10-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06217-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Correction: RhoA balances microglial reactivity and survival during neuroinflammation.

Socodato, Renato / Rodrigues-Santos, Artur / Tedim-Moreira, Joana / Almeida, Tiago O / Canedo, Teresa / Portugal, Camila C / Relvas, João B

Cell death & disease

2023 Volume 14, Issue 12, Page(s) 808

Language	English
Publishing date	2023-12-08
Publishing country	England
Document type	Published Erratum
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06340-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Maternal stress and vulnerability to depression: coping and maternal care strategies and its consequences on adolescent offspring.

Alves, Renata L / Portugal, Camila C / Lopes, Igor M / Oliveira, Pedro / Alves, Cecília J / Barbosa, Fernando / Summavielle, Teresa / Magalhães, Ana

Translational psychiatry

2022 Volume 12, Issue 1, Page(s) 463

Abstract: Depressive mothers often find mother-child interaction to be challenging. Maternal stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to ... ...

Abstract	Depressive mothers often find mother-child interaction to be challenging. Maternal stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depressive-like behavior (Wistar and Kyoto) to investigate the impact of stress (maternal separation-MS) on maternal behavior and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behavior after weaning, while worsening their adolescent offspring cognitive behavior. Whereas MS in Wistar dams elicited higher quality of pup-directed behavior, increasing brain-derived neurotrophic factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to affect the salience of the social environment cues (negatively for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behavior and stress regulatory processes.
MeSH term(s)	Female ; Humans ; Animals ; Rats ; Maternal Deprivation ; Oxytocin ; Depression ; Rats, Wistar ; Maternal Behavior ; Adaptation, Psychological ; Anxiety/psychology ; Stress, Psychological ; Behavior, Animal
Chemical Substances	Oxytocin (50-56-6)
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-022-02220-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Protocol for FRET-Based Live-Cell Imaging in Microglia.

Socodato, Renato / Melo, Pedro / Ferraz-Nogueira, José P / Portugal, Camila C / Relvas, João B

STAR protocols

2020 Volume 1, Issue 3, Page(s) 100147

Abstract: This protocol highlights the use of FRET-based biosensors to investigate signaling events during microglia activation in real time. Understanding microglia activation has gained momentum as it can help decipher signaling mechanisms underlying the ... ...

Abstract	This protocol highlights the use of FRET-based biosensors to investigate signaling events during microglia activation in real time. Understanding microglia activation has gained momentum as it can help decipher signaling mechanisms underlying the neurodegenerative process occurring in neurological disorders. Unlike more traditional methods widely employed in the microglia field, FRET allows microglia signaling events to be studied in real time with exquisite subcellular resolution. However, FRET-based live-cell imaging requires application-specific biosensors and specialized imaging systems, limiting its use in
MeSH term(s)	Biosensing Techniques/methods ; Cell Line ; Diagnostic Imaging ; Fluorescence Resonance Energy Transfer/methods ; Fluorescent Antibody Technique/methods ; Microglia/cytology ; Microglia/metabolism ; Microglia/physiology ; Microscopy, Fluorescence/methods ; Signal Transduction ; Staining and Labeling/methods
Language	English
Publishing date	2020-10-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2020.100147
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The ascorbate transporter SVCT2 to target microglia-dependent inflammation.

Portugal, Camila C / Socodato, Renato / Relvas, João B

Oncotarget

2017 Volume 8, Issue 59, Page(s) 99217–99218

Language	English
Publishing date	2017-11-07
Publishing country	United States
Document type	Editorial
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.22306
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance.

Socodato, Renato / Almeida, Tiago O / Portugal, Camila C / Santos, Evelyn C S / Tedim-Moreira, Joana / Galvão-Ferreira, João / Canedo, Teresa / Baptista, Filipa I / Magalhães, Ana / Ambrósio, António F / Brakebusch, Cord / Rubinstein, Boris / Moreira, Irina S / Summavielle, Teresa / Pinto, Inês Mendes / Relvas, João B

Cell reports

2023 Volume 42, Issue 12, Page(s) 113447

Abstract: Microglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. In this study, we use conditional cell-specific gene targeting in mice with multi-omics approaches and demonstrate that the ... ...

Abstract	Microglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. In this study, we use conditional cell-specific gene targeting in mice with multi-omics approaches and demonstrate that the RhoGTPase Rac1 is an essential requirement for microglia to sense and interpret the brain microenvironment. This is crucial for microglia-synapse crosstalk that drives experience-dependent plasticity, a fundamental brain property impaired in several neuropsychiatric disorders. Phosphoproteomics profiling detects a large modulation of RhoGTPase signaling, predominantly of Rac1, in microglia of mice exposed to an environmental enrichment protocol known to induce experience-dependent brain plasticity and cognitive performance. Ablation of microglial Rac1 affects pathways involved in microglia-synapse communication, disrupts experience-dependent synaptic remodeling, and blocks the gains in learning, memory, and sociability induced by environmental enrichment. Our results reveal microglial Rac1 as a central regulator of pathways involved in the microglia-synapse crosstalk required for experience-dependent synaptic plasticity and cognitive performance.
MeSH term(s)	Microglia/metabolism ; Neuronal Plasticity ; Cognition/physiology ; Animals ; Mice ; Neuropeptides/genetics ; Neuropeptides/physiology ; rac1 GTP-Binding Protein/genetics ; rac1 GTP-Binding Protein/physiology ; Male ; Female ; Mice, Mutant Strains ; Synapses/physiology ; Brain/physiology ; Gene Knockdown Techniques
Chemical Substances	Rac1 protein, mouse ; Neuropeptides ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2023-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113447
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability.

Alves, Renata L / Oliveira, Pedro / Lopes, Igor M / Portugal, Camila C / Alves, Cecília J / Barbosa, Fernando / Summavielle, Teresa / Magalhães, Ana

Scientific reports

2020 Volume 10, Issue 1, Page(s) 13326

Abstract: The development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a ...

Abstract	The development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor.
MeSH term(s)	Adverse Childhood Experiences/psychology ; Animals ; Animals, Newborn/psychology ; Anxiety/complications ; Anxiety/psychology ; Cocaine/adverse effects ; Depression/complications ; Depression/psychology ; Exploratory Behavior/physiology ; Female ; Humans ; Male ; Maternal Deprivation ; Rats ; Rats, Inbred WKY ; Risk Factors ; Stress, Psychological/psychology ; Substance-Related Disorders/etiology ; Substance-Related Disorders/psychology
Chemical Substances	Cocaine (I5Y540LHVR)
Language	English
Publishing date	2020-08-07
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/s41598-020-70242-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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