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Astrocyte-derived TNF and glutamate critically modulate microglia activation by...

Canedo, T; Portugal, CC; Socodato, R; Almeida, TO; Terceiro, AF; Bravo, J; Silva, AI; Magalhães, JD; Guerra-Gomes, S; Oliveira, JF; Sousa, N

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders tri...


A Protocol for FRET-Based Live-Cell Imaging in Microglia

Socodato, R; Melo, PN; Ferraz-Nogueira, JP; Portugal, CC; Relvas, JB

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 ...


Daily alcohol intake triggers aberrant synaptic pruning leading to synapse loss...

Socodato, R; Henriques, JF; Portugal, CC; Almeida, TO; Tedim-Moreira, J; Alves, RL; Canedo, T; Silva, C; Magalhães, A; Summavielle, T; Relvas, JB

Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, wh...


Early-life stress affects drug abuse susceptibility in adolescent rat model ind...

Alves, RL; Oliveira, P; Lopes, IM; Portugal, CC; Alves, CJ; Barbosa, F; Summavielle, T; Magalhães, A

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 vulnerabil...


Microglia Dysfunction Caused by the Loss of Rhoa Disrupts Neuronal Physiology a...

Socodato, R; Portugal, CC; Canedo, T; Rodrigues, A; Almeida, TO; Henriques, JF; Vaz, SH; Magalhães, J; Silva, CM; Baptista, FI; Alves, RL

Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, producing a neurological phenotype (including synapse and neuron loss, impairment of long-term potentiation [LTP], formation of ß-amyloid plaques, and memory ...


Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activatio...

Sousa, NA; Oliveira, GAL; Oliveira, AP; Lopes, ALF; Iles, B; Nogueira, KM; Araújo, TSL; Souza, LKM; Araújo, AR; Ramos-Jesus, J; Plácido, A; Amaral, C

Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVV...


Dopamine-induced ascorbate release from retinal neurons involves glutamate rele...

Portugal, CC; Encarnação, TG; Domith, I; Rodrigues, AS; Oliveira, NA; Socodato, R; Paes-de-carvalho, R

Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the cent...


A mouse model reproducing the pathophysiology of neonatal group B streptococcal...

Andrade, EB; Magalhães, A; Puga, A; Costa, M; Bravo, J; Portugal, CC; Ribeiro, A; Correia-Neves, M; Faustino, A; Firon, A; Trieu-Cuot, P; Summavielle, T

Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. ...


Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in micro...

Portugal, CC; Socodato, R; Canedo, T; Silva, CM; Martins, T; Coreixas, VS; Loiola, EC; Gess, B; Röhr, D; Santiago, AR; Young, P; Minshall, RD

Vitamin C is essential for the development and function of the central nervous system (CNS). The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. SVCT2 specifically transports ascorbate, the reduced form of vitamin C, which acts as a reducing agent. We demonstrated that ascorbate uptake through SVCT2 was critical for the homeostasis of microglia, t...


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