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The IP3R2 knockout mice in behavior: a blessing or a curse?

Gonçalves-Ribeiro, Joana; Vaz, Sandra H.

The inositol 1,4,5-triphosphate receptor type 2 (IP3R2) plays a critical role in intracellular calcium (Ca2+) signaling, particularly in astrocytes, where it mediates Ca2+ release from the endoplasmic reticulum. This mechanism is vital for astrocytic modulation of neuronal networks, impacting synaptic transmission and broader neural circuit functions. The IP3R2 knockout (IP3R2KO) mouse model has been instrument...


Adenosine receptors are the on‐and‐off switch of astrocytic cannabinoid type 1 ...

Gonçalves-Ribeiro, Joana; Savchak, Oksana K.; Pinto, Sara; Gomes, Joana I.; Rivas‐Santisteban, Rafael; Lillo, Alejandro; Sánchez Romero, Javier

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further...


SIGAA: signaling automated analysis: a new tool for Ca2+ signaling quantificati...

Lopes, Rafael Faria; Gonçalves-Ribeiro, Joana; Sebastião, Ana M.; Meneses, Carlos; Vaz, Sandra H.

Astrocytes are non-neural cells, restricted to the brain and spinal cord, whose functions and morphology depend on their location. Astrocyte–astrocyte and astrocyte–neuron interactions occur through cytoplasmic Ca2+ level changes that are assessed to determine cell function and response (i.e., drug testing). The evaluation of alterations in intracellular Ca2+ levels primarily relies on fluorescence imaging tech...


Recovery of depleted miR-146a in ALS cortical astrocytes reverts cell aberranci...

Barbosa, Marta; Gomes, Cátia; Sequeira, Catarina; Gonçalves-Ribeiro, Joana; Pina, Carolina Campos; Carvalho, Luís A.; Moreira, Rui; Vaz, Sandra H.

Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be relea...


Of adenosine and the blues: the adenosinergic system in the pathophysiology and...

Gomes, Joana I.; Farinha Ferreira, Jorge Miguel; Rei, Nádia; Gonçalves-Ribeiro, Joana; Ribeiro, Joaquim A.; Sebastião, Ana M; Vaz, Sandra H.

Major depressive disorder (MDD) is the foremost cause of global disability, being responsible for enormous personal, societal, and economical costs. Importantly, existing pharmacological treatments for MDD are partially or totally ineffective in a large segment of patients. As such, the search for novel antidepressant drug targets, anchored on a clear understanding of the etiological and pathophysiological mech...


Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegener...

Armada-Moreira, Adam; Gomes, Joana I.; Pina, Carolina Campos; Savchak, Oksana K.; Gonçalves-Ribeiro, Joana; Rei, Nádia; Pinto, Sara; Morais, Tatiana P.

Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes si...


Caffeine has a dual influence on NMDA receptor–mediated glutamatergic transmiss...

Silva Martins, Robertta; Rombo, Diogo M.; Gonçalves-Ribeiro, Joana; Meneses, Carlos; Borges-Martins, Vladimir P. P.; Ribeiro, Joaquim A.; Vaz, Sandra H.

Caffeine, a stimulant largely consumed around the world, is a non-selective adenosine receptor antagonist, and therefore caffeine actions at synapses usually, but not always, mirror those of adenosine. Importantly, different adenosine receptors with opposing regulatory actions co-exist at synapses. Through both inhibitory and excitatory high-affinity receptors (A1R and A2R, respectively), adenosine affects NMDA...


Glutamate transporters in hippocampal LTD/LTP: not just prevention of excitotox...

Gonçalves-Ribeiro, Joana; Pina, Carolina Campos; Sebastião, Ana M; Vaz, Sandra H.

Glutamate uptake is a process mediated by sodium-dependent glutamate transporters, preventing glutamate spillover from the synapse. Typically, astrocytes express higher amounts of glutamate transporters, thus being responsible for most of the glutamate uptake; nevertheless, neurons can also express these transporters, albeit in smaller concentrations. When not regulated, glutamate uptake can lead to neuronal de...


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