Raquel Sanchez-Varo

@uma.es

Permanent Professor at Human Physiology, Human Histology, Anatomical Pathology, and Physics and Sport Education Department. Faculty of Medicine
University of Malaga

Raquel Sanchez-Varo


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https://researchid.co/raquelsv

EDUCATION

Bachelor in Biology (University of Seville, 2002)
Bachelor in Biochemistry (University of Seville, 2004)
PhD University of Malaga (2011)

RESEARCH, TEACHING, or OTHER INTERESTS

Histology, Cell Biology, Neuroscience
30

Scopus Publications

Scopus Publications

  • Instagram as a Tool to Improve Human Histology Learning in Medical Education: Descriptive Study
    Alejandro Escamilla-Sanchez, Juan Antonio López-Villodres, Carmen Alba-Tercedor, María Victoria Ortega-Jiménez, Francisca Rius-Díaz, et al.
    Jmir Medical Education, 2025
    Background Student development is currently taking place in an environment governed by new technologies and social media. Some platforms, such as Instagram or X (previously known as “Twitter”), have been incorporated as additional tools for teaching and learning processes in higher education, especially in the framework of image-based applied disciplines, including radiology and pathology. Nevertheless, the role of social media in the teaching of core subjects such as histology has hardly been studied, and there are very few reports on this issue. Objective The aim of this work was to investigate the impact of implementing social media on the ability to learn human histology. For this purpose, a set of voluntary e-learning activities was shared on Instagram as a complement to traditional face-to-face teaching. Methods The proposal included questionnaires based on multiple-choice questions, descriptions of histological images, and schematic diagrams about the subject content. These activities were posted on an Instagram account only accessible by second-year medical students from the University of Malaga. In addition, students could share their own images taken during the laboratory practice and interact with their peers. Results Of the students enrolled in Human Histology 2, 85.6% (143/167) agreed to participate in the platform. Most of the students valued the initiative positively and considered it an adequate instrument to improve their final marks. Specifically, 68.5% (98/143) of the student body regarded the multiple-choice questions and image-based questions as the most useful activities. Interestingly, there were statistically significant differences between the marks on the final exam (without considering other evaluation activities) for students who participated in the activity compared with those who did not or barely participated in the activity (P<.001). There were no significant differences by degree of participation between the more active groups. Conclusions These results provide evidence that incorporating social media may be considered a useful, easy, and accessible tool to improve the learning of human histology in the context of medical degrees.
  • Enhancement of neurogenesis and cognition through intranasal co-delivery of galanin receptor 2 (GALR2) and neuropeptide Y receptor 1 (NPY1R) agonists: a potential pharmacological strategy for cognitive dysfunctions
    Raquel Sánchez-Varo, Alexander López-Salas, Rasiel Beltran-Casanueva, Estela Díaz-Sánchez, Jose Erik Alvarez-Contino, et al.
    Behavioral and Brain Functions, 2024
    Background Spatial memory deficits and reduced neuronal survival contribute to cognitive decline seen in the aging process. Current treatments are limited, emphasizing the need for innovative therapeutic strategies. This research explored the combined effects of intranasally co-administered galanin receptor 2 (GALR2) and neuropeptide Y1 receptor (NPY1R) agonists, recognized for their neural benefits, on spatial memory, neuronal survival, and differentiation in adult rats. After intranasal co-delivery of the GALR2 agonist M1145 and a NPY1R agonist to adult rats, spatial memory was tested with the object-in-place task 3 weeks later. We examined neuronal survival and differentiation by assessing BrdU-IR profiles and doublecortin (DCX) labeled cells, respectively. We also used the GALR2 antagonist M871 to confirm GALR2's crucial role in promoting cell growth. Results Co-administration improved spatial memory and increased the survival rate of mature neurons. The positive effect of GALR2 in cell proliferation was confirmed by the nullifying effects of its antagonist. The treatment boosted DCX-labeled newborn neurons and altered dendritic morphology, increasing cells with mature dendrites. Conclusions Our results show that intranasal co-delivery of GALR2 and NPY1R agonists improves spatial memory, boosts neuronal survival, and influences neuronal differentiation in adult rats. The significant role of GALR2 is emphasized, suggesting new potential therapeutic strategies for cognitive decline.
  • Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease
    Miriam Bettinetti‐Luque, Laura Trujillo‐Estrada, Eduardo Garcia‐Fuentes, Juana Andreo‐Lopez, Raquel Sanchez‐Varo, et al.
    British Journal of Pharmacology, 2024
    Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age‐related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood–brain barrier to reach the target areas in the brain or to regulate the function of the blood–brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood–brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential.
  • Microbiome Alterations and Alzheimer’s Disease: Modeling Strategies with Transgenic Mice
    Juan Antonio López-Villodres, Alejandro Escamilla, Silvia Mercado-Sáenz, Carmen Alba-Tercedor, Luis Manuel Rodriguez-Perez, et al.
    Biomedicines, 2023
    In the last decade, the role of the microbiota–gut–brain axis has been gaining momentum in the context of many neurodegenerative and metabolic disorders, including Alzheimer’s disease (AD) and diabetes, respectively. Notably, a balanced gut microbiota contributes to the epithelial intestinal barrier maintenance, modulates the host immune system, and releases neurotransmitters and/or neuroprotective short-chain fatty acids. However, dysbiosis may provoke immune dysregulation, impacting neuroinflammation through peripheral–central immune communication. Moreover, lipopolysaccharide or detrimental microbial end-products can cross the blood–brain barrier and induce or at least potentiate the neuropathological progression of AD. Thus, after repeated failure to find a cure for this dementia, a necessary paradigmatic shift towards considering AD as a systemic disorder has occurred. Here, we present an overview of the use of germ-free and/or transgenic animal models as valid tools to unravel the connection between dysbiosis, metabolic diseases, and AD, and to investigate novel therapeutical targets. Given the high impact of dietary habits, not only on the microbiota but also on other well-established AD risk factors such as diabetes or obesity, consistent changes of lifestyle along with microbiome-based therapies should be considered as complementary approaches.
  • Correction to: Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease (Acta Neuropathologica, (2019), 138, 2, (251-273), 10.1007/s00401-019-02013-z)
    Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Juan García-Revilla, Yiyi Yang, et al.
    Acta Neuropathologica, 2023
  • Animal and Cellular Models of Alzheimer’s Disease: Progress, Promise, and Future Approaches
    Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Raquel Sanchez-Varo, Juan Antonio Garcia-Leon, Cristina Nuñez-Diaz, et al.
    Neuroscientist, 2022
    Alzheimer’s disease (AD) is an incurable neurodegenerative disease affecting over 45 million people worldwide. Transgenic mouse models have made remarkable contributions toward clarifying the pathophysiological mechanisms behind the clinical manifestations of AD. However, the limited ability of these in vivo models to accurately replicate the biology of the human disease have precluded the translation of promising preclinical therapies to the clinic. In this review, we highlight several major pathogenic mechanisms of AD that were discovered using transgenic mouse models. Moreover, we discuss the shortcomings of current animal models and the need to develop reliable models for the sporadic form of the disease, which accounts for the majority of AD cases, as well as human cellular models to improve success in translating results into human treatments.
  • Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis
    Raquel Sanchez-Varo, Marina Mejias-Ortega, Juan Jose Fernandez-Valenzuela, Cristina Nuñez-Diaz, Laura Caceres-Palomo, et al.
    International Journal of Molecular Sciences, 2022
    Alzheimer’s disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling battery.
  • Plaque-Associated Oligomeric Amyloid-Beta Drives Early Synaptotoxicity in APP/PS1 Mice Hippocampus: Ultrastructural Pathology Analysis
    Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, Juan Jose Fernandez-Valenzuela, Vanessa De Castro, Marina Mejias-Ortega, et al.
    Frontiers in Neuroscience, 2021
    Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. In this sense, synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease. At the histopathological level, post mortem AD brains typically exhibit intraneuronal neurofibrillary tangles (NFTs) along with the accumulation of amyloid-beta (Abeta) peptides in the form of extracellular deposits. Specifically, the oligomeric soluble forms of Abeta are considered the most synaptotoxic species. In addition, neuritic plaques are Abeta deposits surrounded by activated microglia and astroglia cells together with abnormal swellings of neuronal processes named dystrophic neurites. These periplaque aberrant neurites are mostly presynaptic elements and represent the first pathological indicator of synaptic dysfunction. In terms of losing synaptic proteins, the hippocampus is one of the brain regions most affected in AD patients. In this work, we report an early decline in spatial memory, along with hippocampal synaptic changes, in an amyloidogenic APP/PS1 transgenic model. Quantitative electron microscopy revealed a spatial synaptotoxic pattern around neuritic plaques with significant loss of periplaque synaptic terminals, showing rising synapse loss close to the border, especially in larger plaques. Moreover, dystrophic presynapses were filled with autophagic vesicles in detriment of the presynaptic vesicular density, probably interfering with synaptic function at very early synaptopathological disease stages. Electron immunogold labeling showed that the periphery of amyloid plaques, and the associated dystrophic neurites, was enriched in Abeta oligomers supporting an extracellular location of the synaptotoxins. Finally, the incubation of primary neurons with soluble fractions derived from 6-month-old APP/PS1 hippocampus induced significant loss of synaptic proteins, but not neuronal death. Indeed, this preclinical transgenic model could serve to investigate therapies targeted at initial stages of synaptic dysfunction relevant to the prodromal and early AD.
  • Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer's disease
    Maria V. Sanchez‐Mico, Sebastian Jimenez, Angela Gomez‐Arboledas, Clara Muñoz‐Castro, Carmen Romero‐Molina, et al.
    GLIA, 2021
    Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid‐β plaques in Alzheimer's disease (AD). We have previously shown that reactive astrocytes enwrap, phagocytose, and degrade dystrophic synapses in the hippocampus of APP mice and AD patients, but affecting less than 7% of dystrophic neurites, suggesting reduced phagocytic capacity of astrocytes in AD. Here, we aimed to gain insight into the underlying mechanisms by analyzing the capacity of primary astrocyte cultures to phagocytose and degrade isolated synapses (synaptoneurosomes, SNs) from APP (containing dystrophic synapses and amyloid‐β peptides), Tau (containing AT8‐ and AT100‐positive phosphorylated Tau) and WT (controls) mice. We found highly reduced phagocytic and degradative capacity of SNs‐APP, but not AT8/AT100‐positive SNs‐Tau, as compared with SNs‐WT. The reduced astrocyte phagocytic capacity was verified in hippocampus from 12‐month‐old APP mice, since only 1.60 ± 3.81% of peri‐plaque astrocytes presented phagocytic structures. This low phagocytic capacity did not depend on microglia‐mediated astrocyte reactivity, because removal of microglia from the primary astrocyte cultures abrogated the expression of microglia‐dependent genes in astrocytes, but did not affect the phagocytic impairment induced by oligomeric amyloid‐β alone. Taken together, our data suggest that amyloid‐β, but not hyperphosphorylated Tau, directly impairs the capacity of astrocytes to clear the pathological accumulation of oligomeric amyloid‐β, as well as of peri‐plaque dystrophic synapses containing amyloid‐β, perhaps by reducing the expression of phagocytosis receptors such as Mertk and Megf10, thus increasing neuronal damage in AD. Therefore, the potentiation or recovery of astrocytic phagocytosis may be a novel therapeutic avenue in AD.
  • Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model
    Juan Jose Fernandez-Valenzuela, Raquel Sanchez-Varo, Clara Muñoz-Castro, Vanessa De Castro, Elisabeth Sanchez-Mejias, et al.
    Scientific Reports, 2020
    In Alzheimer’s disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology.
  • Human pluripotent stem cell-derived neural cells as a relevant platform for drug screening in alzheimer’s disease
    Juan Antonio Garcia-Leon, Laura Caceres-Palomo, Elisabeth Sanchez-Mejias, Marina Mejias-Ortega, Cristina Nuñez-Diaz, et al.
    International Journal of Molecular Sciences, 2020
  • Editorial: Risk Factors for Alzheimer's Disease
    Ines Moreno-Gonzalez, Rodrigo Morales, David Baglietto-Vargas, Raquel Sanchez-Varo
    Frontiers in Aging Neuroscience, 2020
  • Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer's mice and patients
    Elisabeth Sanchez‐Mejias, Cristina Nuñez‐Diaz, Raquel Sanchez‐Varo, Angela Gomez‐Arboledas, Juan Antonio Garcia‐Leon, et al.
    Brain Pathology, 2020
  • Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
    Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Juan García-Revilla, Yiyi Yang, et al.
    Acta Neuropathologica, 2019
  • Distinct microglial responses in two transgenic murine models of TAU pathology
    Carmen Romero-Molina, Victoria Navarro, Raquel Sanchez-Varo, Sebastian Jimenez, Juan J. Fernandez-Valenzuela, et al.
    Frontiers in Cellular Neuroscience, 2018
  • Microglia in Alzheimer's disease: Activated, dysfunctional or degenerative
    Victoria Navarro, Elisabeth Sanchez-Mejias, Sebastian Jimenez, Clara Muñoz-Castro, Raquel Sanchez-Varo, et al.
    Frontiers in Aging Neuroscience, 2018
  • Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
    Angela Gomez-Arboledas, Jose C. Davila, Elisabeth Sanchez-Mejias, Victoria Navarro, Cristina Nuñez-Diaz, et al.
    GLIA, 2018
  • Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer's disease
    David Baglietto-Vargas, Elisabeth Sánchez-Mejias, Victoria Navarro, Sebastián Jimenez, Laura Trujillo-Estrada, et al.
    Scientific Reports, 2017
  • Glutaminase and MMP-9 downregulation in cortex and hippocampus of LPA1 receptor null mice correlate with altered dendritic spine plasticity
    Ana Peñalver, José A. Campos-Sandoval, Eduardo Blanco, Carolina Cardona, Laura Castilla, et al.
    Frontiers in Molecular Neuroscience, 2017
  • Soluble phospho-tau from Alzheimer’s disease hippocampus drives microglial degeneration
    Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Maria Sanchez-Mico, Raquel Sanchez-Varo, et al.
    Acta Neuropathologica, 2016
  • In vivo modification of Abeta plaque toxicity as a novel neuroprotective lithium-mediated therapy for Alzheimer's disease pathology
    Acta Neuropathologica Communications, 2014
  • Early neuronal loss and axonal/presynaptic damage is associated with accelerated amyloid-β accumulation in AβPP/PS1 Alzheimer's disease mice subiculum
    Laura Trujillo-Estrada, José Carlos Dávila, Elisabeth Sánchez-Mejias, Raquel Sánchez-Varo, Angela Gomez-Arboledas, et al.
    Journal of Alzheimer S Disease, 2014
  • Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus
    Manuel Torres, Sebastian Jimenez, Raquel Sanchez-Varo, Victoria Navarro, Laura Trujillo-Estrada, et al.
    Molecular Neurodegeneration, 2012
  • Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer's mice hippocampus
    Raquel Sanchez-Varo, Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Manuel Torres, David Baglietto-Vargas, et al.
    Acta Neuropathologica, 2012
  • Age-dependent accumulation of soluble amyloid β (Aβ) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-α (sAPPα) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK- 3β pathway in Alzheimer mouse model
    Sebastian Jimenez, Manuel Torres, Marisa Vizuete, Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, et al.
    Journal of Biological Chemistry, 2011
  • Calretinin interneurons are early targets of extracellular amyloid-β pathology in PS1/AβPP Alzheimer mice hippocampus
    David Baglietto-Vargas, Ines Moreno-Gonzalez, Raquel Sanchez-Varo, Sebastian Jimenez, Laura Trujillo-Estrada, et al.
    Journal of Alzheimer S Disease, 2010
  • Extracellular amyloid-β and cytotoxic glial activation induce significant entorhinal neuron loss in young PS1M146L/APP751SL mice
    Ines Moreno-Gonzalez, David Baglietto-Vargas, Raquel Sanchez-Varo, Sebastian Jimenez, Laura Trujillo-Estrada, et al.
    Journal of Alzheimer S Disease, 2009
  • Inflammatory response in the hippocampus of PS1M146L/APP 751SL mouse model of Alzheimer's disease: Age-dependent switch in the microglial phenotype from alternative to classic
    Sebastian Jimenez, David Baglietto-Vargas, Cristina Caballero, Ines Moreno-Gonzalez, Manuel Torres, et al.
    Journal of Neuroscience, 2008
  • Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus: Potential relation with the loss of somatostatin GABAergic neurons
    M. Paz Gavilán, Elisa Revilla, Cristina Pintado, Angélica Castaño, M. Luisa Vizuete, et al.
    Journal of Neurochemistry, 2007
  • Inter-individual variability in the expression of the mutated form of hPS1M146L determined the production of Aβ peptides in the PS1xAPP transgenic mice
    Cristina Caballero, Sebastian Jimenez, Ines Moreno‐Gonzalez, David Baglietto‐Vargas, Raquel Sanchez‐Varo, et al.
    Journal of Neuroscience Research, 2007