Ph.D. in Neuroscience and Nutrition
Scientific Research Experience
2018-2022
Ph.D. Dissertation topic:
“Investigating the involvement of brain tryptophan metabolism in obesity-induced memory deficits”.
Thesis supervisor: Dr. Francisco Bolaños
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UMR 1280 - Physiologie des Adaptations Nutritionnelles. INRAe. Nantes, France.
Obesity has a detrimental impact in the memory and learning capacities, affecting men and women. Moreover, studies in humans and animals have pointed out that the descendants of obese parents are more prone to develop learning disabilities. Although the mechanisms involved in these memory deficits have not been fully described, we proposed that alterations in the tryptophan (Trp) metabolism play an important role. Trp is an essential amino acid that gives rise to neuroactive molecules that control the construction of memories.
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Trp is metabolized by the indole, serotonin and kynurenine pathways. The kynurenine pathway produces kynurenic acid (KA) and quinolinic acid (QA), which are considered as neuroprotective and neurotoxic components, respectively. Both metabolites regulate the glutamatergic signaling, while KA is an antagonist of NMDA and AMPA receptors, QA is an agonist of NMDA receptors. Therefore, both molecules play an important role in the modulation of Long-term Potentiation and Long-term Depression, the cellular processes involved in learning and memory formation.
An increment in the KA or QA concentrations can trigger alterations in neurotransmitters availability, cytotoxicity or cell death. Interestingly, an increase in KA or QA has been described in several psychiatric and neurodegenerative diseases and this is thought to be a consequence of the neuroinflammatory state of the patients. Since obesity causes a chronic low-grade inflammatory state, we claimed that this could lead to alterations in the brain Trp-metabolism, and then provoke memory impairment.
Findings:
In a Wistar-rat model fed with a free-choice high fat / high sugar diet we shown that obesity promotes neuroinflammation, memory and learning deficits, and altered brain TRP metabolism. While obese males had accumulation of QA in the hippocampus (See the first published article), obese females presented a reduction in TRP levels, as well as in the levels of metabolites derived from this amino acid in both, the hippocampus and frontal cortex; these changes were dependent on the oestrous cycle (See the second published article).
In the offspring of either obese mothers or obese fathers, we have also found memory deficiencies and alterations in the central-TRP metabolism. These data will be published soon.
Laboratory techniques used
Molecular Biology
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PCR primers design
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RNA extraction and cDNA obtention
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RT-PCR
Cell biology
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Primary culture of glial cells
Immunocytochemistry
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Detection of microglia and astrocytes
Animal experimentation
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Sexual behavior and mating of rats
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Determination of the estrous cycle phases
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Behavioral tests
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Elevated Plus Maze test
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Y maze test
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Open Field test
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Novel Object Recognition test
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Novel Object Location test
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Analytical techniques
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Liquid Chromatography with tandem mass spectrometry​
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2014-2016
MSc. Dissertation topic:
“ Anti-obesity effect of three Tabebuia rosea extracts in a murine model ”
Thesis supervisor: Dr. Cynthia Ordaz Pichardo († 2022)
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Laboratory of Cell Biology and Natural Products. National School of Medicine and Homeopathy. IPN. Mexico City.
Thesis supervisor: Dr. Laurence Annie Marchat Marchau
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Laboratory of Biomedicine. National School of Medicine and Homeopathy. IPN. Mexico City.
Obesity is defined as the excessive fat accumulation that might impair health. This complex disease is considered by the WHO as a major public health problem.
Although there are different pharmacological treatments to counteract the obesity progression, patients cannot take them for long periods of time because they may have side effects that are not favorable to their health. For this reason, it is necessary to look for new alternatives to prevent obesity without causing adverse effects and providing long-term results.
The use of traditional medicine for the treatment of obesity has increased. One of the alternatives is herbal medicine for which there is scientific evidence that proves its therapeutic properties. The objective of this project was to demonstrate the anti-obesity effect of three extracts obtained from the bark of the Tabebuia rosea tree in a murine model of obesity.
The bark extracts were obtained by using ethanol, ethyl acetate and hexane as solvents to acquire metabolites with a great chemical diversity. The presence of alkaloids, terpenes, phenolic compounds, and coumarins, among others was identified. The bark extracts were subjected to the Ames test to demonstrate that they did not produce mutations due to frameshift, base substitution, or oxidative damage in the DNA.
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Mice of the C57BL/6J strain were fed with a high-fat diet for six weeks in order to induce obesity. Subsequently, mice were orally supplemented with the different bark extracts for eight weeks while continuing to consume the high-fat diet. The results showed that T. rosea extracts prevented body weight gain and improved peripheral glucose levels.
Laboratory techniques used
Phytochemistry
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Maceration
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Thin layer chromatography
Mutagenicity test
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Ames test
Animal experimentation
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Orogastric administration of treatments
Protein analyses
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Western Blot
2010-2012
BSc. Dissertation topic:
"Molecular characterization of the Peptidil-tRNA hydrolases from Entamoeba histolytica".
Thesis supervisor: Dr. Gloria León.
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Laboratory of Zoology. National School of Biological Sciences. IPN. Mexico City, Mexico.
During the translation process some peptidyl-tRNA complexes are prematurely released from the ribosomes before reaching the stop codon, an event called "drop off". In these cases, peptidyl-tRNA hydrolase (Pth) enzymes dissociate peptidyl-tRNA complexes to allow the free-tRNAs to join the protein synthesis process. The aim of this project was to confirm the presence of the Pth enzymes in the intestinal parasite Entamoeba histolytica. In addition, the three-dimensional modeling of those enzymes was performed.
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Laboratory techniques used
Molecular Biology
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Ligation inserts in the vector pPROEX-1
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Enzymatic restriction
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RT-PCR
Microbiology techniques
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Bacterial culture
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Preparation and transformation of competent cells
Bioinformatics analysis
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BLAST
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Identification of conserved domains in the Pfam site of the Sanger Institute.
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Three-dimensional modeling of enzymes by using the platforms Modeller, I-Tasser and Swiss Model.