João Laranjinha

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Nitric oxide (*NO) is a ubiquitous signaling molecule that participates in the neuromolecular phenomena associated with memory formation. In the hippocampus, neuronal *NO production is coupled to the activation of the NMDA-type of glutamate receptor. Although *NO-mediated signaling has been associated with soluble guanylate cyclase activation, cytochrome(More)
The increase in life expectancy is accompanied by an increased risk of developing neurodegenerative disorders and age is the most relevant risk factor for the appearance of cognitive decline. While decreased neuronal count has been proposed to be a major contributing factor to the appearance of age-associated cognitive decline, it appears to be insufficient(More)
Nitric oxide (*NO) production in response to stimulation of the NMDA glutamate receptor is implicated not only in the synaptic plasticity in hippocampus but may also participate in excitotoxic cell death. Using *NO-selective microssensors inserted into the diffusional field of *NO in acute hippocampal slices, we describe the *NO concentration dynamics(More)
During the last two decades nitric oxide (.NO) gas has emerged as a novel and ubiquitous intercellular modulator of cell functions. In the brain, .NO is implicated in mechanisms of synaptic plasticity but it is also involved in cell death pathways underlying several neurological diseases. Because of its hydrophobicity, small size, and rapid diffusion(More)
The understanding of the unorthodox actions of neuronal-derived nitric oxide ((•)NO) in the brain has been constrained by uncertainties regarding its quantitative profile of change in time and space. As a diffusible intercellular messenger, conveying information associated with its concentration dynamics, both the synthesis via glutamate stimulus and(More)
During the last decades nitric oxide ((•)NO) has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain. (•)NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual(More)
Nitric oxide (NO(*)) is a diffusible regulatory molecule involved in a wide range of physiological and pathological events. At the tissue level, a local and temporary increase in NO(*) concentration is translated into a cellular signal. From our current knowledge of biological synthesis and decay, the kinetics and mechanisms that determine NO(*)(More)
The coupling between neuronal activity and cerebral blood flow (CBF) is essential for normal brain function. The mechanisms behind this neurovascular coupling process remain elusive, mainly because of difficulties in probing dynamically the functional and coordinated interaction between neurons and the vasculature in vivo. Direct and simultaneous(More)
The reversible redox conversion of nitrite and nitric oxide ((•)NO) in a physiological setting is now widely accepted. Nitrite has long been identified as a stable intermediate of (•)NO oxidation but several lines of evidence support the reduction of nitrite to nitric oxide in vivo. In the gut, this notion implies that nitrate from dietary sources fuels the(More)
Nitric oxide ((•)NO) is a labile endogenous free radical produced upon glutamatergic neuronal activity in hippocampus by neuronal nitric oxide synthase (nNOS), where it acts as a modulator of both synaptic plasticity and cell death associated with neurodegeneration. The low CNS levels and fast time dynamics of this molecule require the use of rapid(More)