Ana Velasco

• University of Salamanca

Introduction Multiple sclerosis (MS) is a progressive disease with a fluctuating and unpredictable course that has no curative treatment at present. One of its main characteristics is the variety of signs and symptoms that produce a high percentage of patients who present alterations in balance and gait during the development of the disease, decrea...

Amyloid-β (Aβ) peptides, Aβ40, Aβ42, and recently Aβ25 - 35, have been directly implicated in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that all three peptides decrease neuronal viability, but Aβ40 also promotes synaptic disassembling. In this work, we have studied the effects of these peptides on astrocytes in primary...

Aberrant formation of the cerebral cortex could be attributed to the lack of suitable substrates that direct the migration of neurons. Previous work carried out at our laboratory has shown that oleic acid is a neurotrophic factor. In order to characterize the effect of oleic acid in a cellular model of Down’s syndrome (DS), here, we used immortaliz...

Western blot images of the effect of amyloid-beta peptides on synaptophysin (Syp) expression in the absence or the presence of HSA. Neurons in primary culture (3 DIV) were incubated for 20 h in DMEM medium with three different Aβ peptides: Aβ25-35, Aβ40, or Aβ42 (30 μM) in the absence or the presence of HSA (30 μM) or as HSA-Aβ complexes (30 μM). T...

Effect of amyloid-beta peptides and HSA on PSD-95 and synaptotagmin localization. Neurons in primary culture (4 DIV) were incubated for 2 h in Hanks medium in the absence or the presence of 30 μM Aβ25-35, Aβ40, or Aβ42 and in the absence or the presence of 30 μM HSA. After incubation, cells were fixed and immunocytochemistry against PSD-95 (in gree...

Cell viability dose-response curves of neurons in primary culture against different amyloid-beta peptides. Neurons in primary culture (3 DIV) were incubated for 20 h in the presence of increasing concentrations of Aβ25-35, Aβ40, or Aβ42. Results are expressed as percentages compared to non-treated cells and are means ± SEM (n ≥ 5). b value is the s...

Effect of HSA on amyloid-beta cell entry. Neurons in primary culture (3 DIV) were incubated for 2 h in Hanks medium in the presence of 30 μM of Aβ40 or Aβ42, and HSA (30 μM). After incubation, cells were fixed and immunocytochemistry against glucose transporter 3 (in red) and against AβPP (in green) was carried out. Nuclei were stained with TOPRO (...

Amyloid-β (Aβ), Aβ40, Aβ42, and, recently, Aβ25-35 have been directly implicated in the pathogenesis of Alzheimer’s disease. We have studied the effects of Aβ on neuronal death, reactive oxygen species (ROS) production, and synaptic assembling in neurons in primary culture. Aβ25-35, Aβ40, and Aβ42 significantly decreased neuronal viability, althoug...

The synthesis and release of the neurotrophic factor oleic acid requires internalization of albumin into the astrocyte, which is mediated by megalin. In this study, we show that the binding and internalization of albumin involve its interaction with megalin, caveolin-1, caveolin-2 and cavin, but not with clathrin in astrocytes from primary culture....

Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is us...

We have previously shown that the uptake and transcytosis of albumin in astrocytes promote the synthesis of the neurotrophic factor oleic acid. Although the mechanism by which albumin induces oleic acid synthesis is well known, the mechanism of albumin uptake in astrocytes remains unknown. In this work, we found that astrocytes express megalin, an...

We have shown recently that the presence of albumin in astrocytes triggers the synthesis and release of oleic acid, which behaves as a neurotrophic factor for neurons. Thus, oleic acid promotes axonal growth together with the expression of the axonal growth-associated protein, GAP-43. Here we attempted to elucidate whether the neurotrophic effect o...

We have recently reported that albumin, a serum protein present in the developing brain, stimulates the synthesis of oleic acid by cultured astrocytes by inducing stearoyl-CoA 9-desaturase, the rate-limiting enzyme in oleic acid synthesis, through activation of the sterol regulatory element-binding protein-1. In this work, we offer evidence support...

We have recently reported that albumin, a serum protein present in the developing brain, stimulates the synthesis of oleic acid by astrocytes, which promotes neuronal differentiation. In this work, we gain insight into the mechanism by which albumin induces the synthesis of this neurotrophic factor. Our results show that astrocytes internalize albu...

We have previously shown that several gap junction uncouplers increase the uptake of glucose in astrocytes. The aim of the present work was to study whether the increase in glucose uptake was a consequence of the inhibition of gap junction communication and the purpose of this effect. Our results show that alpha-glycyrrhetinic acid and endothelin-1...

Using the scrape-loading technique in cultured astrocytes, we show that sulfonylureas such as tolbutamide and glybenzcyclamide, which inhibit the ATP-sensitive K+ channel, prevent the inhibition of gap junction permeability caused by several structurally unrelated uncouplers such as oleic acid, arachidonic acid, endothelin-1, octanol, and α-glycyrr...