Sónia Sá Santos

Research Institute for Medicines (iMed.ULisboa) · Stem Cell Bioenergetics and Neuroregeneration Group

Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/pr...

This study investigates the effect of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, on postnatal neurogenesis in the subventricular zone (SVZ) via the non-classical cannabinoid receptor TRPV1. Using the neurosphere assay, we found that CBDV promotes cell survival, cell proliferation, and neuronal differentiation of neural stem/progenitor c...

Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative...

The influence of dietary factors on brain health and mental function is becoming increasingly recognized. Similarly, mounting evidence supports a role for gut microbiota in modulating central nervous system function and behaviour. Still, the molecular mechanisms responsible for the impact of diet and associated microbiome in adult neurodegeneration...

Recent evidence suggests that neural stem cell (NSC) fate is highly dependent on mitochondrial bioenergetics. Tauroursodeoxycholic acid (TUDCA), an endogenous neuroprotective bile acid and a metabolic regulator, stimulates NSC proliferation and enhances adult NSC pool in vitro and in vivo. In this study, we dissected the mechanism triggered by this...

The endogenous peptide kyotorphin (KTP) has been extensively studied since it was discovered in 1979. The dipeptide is distributed unevenly over the brain but the majority is concentrated in the cerebral cortex. The putative KTP receptor has not been identified yet. As many other neuropeptides, KTP clearance is mediated by extracellular peptidases...

Kyotorphin (KTP) is an endogenous peptide with analgesic properties when administered into the central nervous system (CNS). Its amidated form (L-Tyr-L-Arg-NH2; KTP-NH2) has improved analgesic efficacy after systemic administration, suggesting blood-brain barrier (BBB) crossing. KTP-NH2 also has anti-inflammatory action impacting on microcirculatio...

Amidated kyotorphin (L-Tyr-L-Arg-NH2; KTP-NH2) has analgesic properties following systemic administration. Although KTP-NH2 does not have toxic effects in the liver, its biodistribution is unknown. KTP-NH2 was radioiodinated to evaluate its biological fate in vivo. Mono-radioiodinated KTP-NH2 ([125I]MIK) was radiochemically stable in vitro, namely...

Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer’s disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an e...

In Alzheimer's disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP)...

The adverse side-effects associated with opioid administration restrain their use as analgesic drugs and call for new solutions to treat pain. Two kyotorphin derivatives, kyotorphin-amide (KTP-NH2) and ibuprofen-KTP-NH2 (IbKTP-NH2) are promising alternatives to opioids: they trigger analgesia via an indirect opioid mechanism and are highly effectiv...

IntroductionPeptides as Future Drug CandidatesCentral Nervous System Analgesic PeptidesEndogenous Opioid SystemStrategies to Deliver Analgesic Peptides to the BrainDevelopment of New Opioid-Derived PeptidesKyotorphin – the Potential of an Endogenous DipeptideNew KTP DerivativesAssessing BBB Permeability with Peptide – Membrane Partition StudiesKyot...

The presence of purines and pyrimidines bases, nucleosides, and nucleotides in the culture medium has shown to differently affect the growth of a Chinese hamster ovary (CHO) cell line producing the secreted form of the human placental alkaline phosphatase enzyme (SEAP; Carvalhal et al., Biotech Prog. 2003;19:69-83). CHO, BHK, as well as Sf9 cell gr...

A metabolic flux analysis (MFA) study was performed to infer about the metabolic plasticity of astrocytes when exposed to two environmental stresses. In the first study an astrocytic culture was subjected to a hypoglycemic period of 24 h and the metabolic response was investigated during and after the insult. The second study involved another astro...

In this work, brain cell metabolism was investigated by (13)C NMR spectroscopy and metabolic flux analysis (MFA). Monotypic cultures of astrocytes were incubated with labeled glucose for 38 h, and the distribution of the label was analyzed by (13)C NMR spectroscopy. The analysis of the spectra reveals two distinct physiological states characterized...

We report a study on neural metabolism of long-term three-dimensional cultures of rat embryonic brain cells in stirred vessels. Our experimental setup was optimized to keep viable aggregate cultures with neuronal maintenance for up to 44 days. Results show that aggregate size and shape could be hydrodynamically controlled depending on the impeller...

The production of retroviral vectors by human cell lines is still hampered by low titers making it relatively difficult to produce very large quantities of this vector of high interest for clinical gene therapy applications. Thus, to improve vector production, we studied the influence of different sugars alone or combinations of sugars on cell grow...

Diminished activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), an important component of the tricarboxylic acid (TCA) cycle, occurs in several neurological diseases. The effect of specific KGDHC inhibitors [phosphonoethyl ester of succinyl phosphonate (PESP) and the carboxy ethyl ester of succinyl phosphonate (CESP)] on [1-13C]glucos...

We report the first approach for growth and maintenance of primary astrocytes on a fully controlled environment. For this purpose, cells were immobilized in Cytodex microcarriers and grown in a stirred tank bioreactor. The distribution of astrocytes at the microcarrier surface was visualized using confocal microscopy and glial fibrillary acidic pro...

Arresting cell growth and thus decreasing cell division potentially lessens the chance for genetic drift in the cell population; this would be of utmost importance for the consistent production of biopharmaceuticals during long periods. The drawback of the addition of well-known synchronizing agents, such as chemotherapeutics, is that they cause a...

Arresting cell growth and thus decreasing cell division potentially lessens the chance for genetic drift in the cell population: this would be of utmost importance for the consistent production of high quality products. Cell growth arrest of two industrially relevant animal cell lines (CHO and BHK cells) has been successfully achieved by the overex...