Mariana Vargas Caballero is a Mexican researcher currently working at the University of Southampton, where she leads a laboratory dedicated to understand the role of communication between neurons and how these are affected by diseases like Alzheimer.
In an interview with the News Agency of the National Council for Science and Technology (CONACYT), the scientist talked about the research models used to answer fundamental questions about the formation of memories, the connection between neurons and the mechanisms that govern plasticity between cells, particularly in relation to Alzheimer’s disease.
Mariana Vargas, along with postdoctoral researcher Ksenia Kurbatskaya and graduate student Luis Guevara Mendoza, have developed research lines to know the factors that lead to Alzheimer’s disease in culture dishes, animal models and human neurons
Within these lines, they have become pioneer researchers in the use and collection of human brain tissue discarded from neurosurgeries. Thus, the experiments and developed drugs can be tested in directly human tissue to know the positive or negative effects on the function of human neural networks.
“The tissue we obtain, with informed consent of patients, is connected in the operating room and transported to the laboratory for studies with live neurons, where we can get information on experiments on pharmacology and fundamental biology of neurons,” said Mariana Vargas, who holds a PhD in neuroscience from the University of Cambridge.
The importance of being able to uses discarded human tissue for experimentation is because many valid discoveries made in mouse models are not applicable or successful when transferred to humans in clinical trials, because there are significant differences between both. These differences could represent the reason why many drugs have failed in clinical trials. For example, humans have two essential proteins characteristic of Alzheimer’s’ disease: tau and beta amyloid. Although they also exist in mouse models of the disease, there are important differences: the number of tau isoforms in human adults are six, compared to three isoforms in mouse models.
“That’s why our basic research in mice […] may not take into account the great differences between species, being likely that the resulting drug, produced after years of research and financial investment, could fail,” she said.
Vargas published in 2016 a deep review on this issue with her colleagues. However, she described that it is possible to continue using mice as degenerative model to understand how synapses and memory in Alzheimer’s disease are affected. Especially in the early stages when memory loss is not yet clear but the damage to neural circuits has already begun, one of the routes that maybe can help develop successful future drugs.
To do this, it will also be necessary to incorporate certain checkpoints and validation in human brain tissue that could be used to confirm that the drugs designed function as they did in the mice, ensuring it will be effective when applied to people.
To obtain these tissues, the Mexican researcher established a collaboration agreement with neurosurgeons of Wessex Neurological Center in England; who, through ethical and granting permits, obtain informed consent to collect previously wasted tissue from patients who undergo brain surgery. For example, in individuals with drug-resistant epilepsy, it is recommended remove the sclerotic hippocampus and part of the cerebral cortex must be removed to access that structure.
Due to the reasons why these tissues are obtained, it is important to know whether this material is healthy or not to know if it can serve as brain model in its more efficiently form. To resolve this issue, Caballero Vargas’ laboratory checks its level of functionality. “We have to find ways to use it because it is the most normal human tissue with which we can experiment“. To check its functionality is, for example, the part of the hippocampus of a patient who has sclerosis is tested for biomarkers of inflammation.
Although this new model is mainly focused on finding solutions to Alzheimer’s disease, the researchers think it could be use in other neurological diseases.
Source: News Agency CONACYT