Browsing by Author "Cornejo, Francisca"

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    Comparative Efficacy of a High-Dose vs Standard-Dose Hepatitis B Revaccination Schedule Among Patients With HIV A Randomized Clinical Trial
    (2021) Vargas, Jose Ignacio; Jensen, Daniela; Martinez, Felipe; Sarmiento, Valeska; Peirano, Felipe; Acuna, Pedro; Provoste, Felipe; Bustos, Valentina; Cornejo, Francisca; Fuster, Antonieta; Acuna, Martin; Fuster, Felipe; Soto, Sabrina; Estay, Denisse; Jensen, Werner; Ahumada, Rodrigo; Arab, Juan Pablo; Soza, Alejandro; Fuster, Francisco
    IMPORTANCE Active immunization for hepatitis B virus (HBV) infection is recommended in patients living with HIV. Limited evidence is available about the most appropriate regimen of HBV vaccination among those who have not responded to an initial schedule.
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    Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice
    (2024) Cortés, Bastián I.; Meza, Rodrigo C.; Ancatén-González, Carlos; Ardiles, Nicolás M.; Aránguiz, María-Ignacia; Tomita, Hideaki; Kaplan, David R.; Cornejo, Francisca; Nunez-Parra, Alexia; Moya, Pablo R.; Chávez, Andrés E.; Cancino, Gonzalo I.
    Background: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown. Results: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety. Conclusions: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.
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    Ptprd deficiency promotes tau hyperphosphorylation and impairs cognitive function in aged mice
    (Springer Nature, 2025) Foncea, Analía; Franchini, Nayhara; Tobar, Isidora; Thienel, Sebastián; Retamal, Ignacio N.; Cancino Lobos, Gonzalo; Cornejo, Francisca
    Background Tau phosphorylation is a tightly regulated process that ensures proper neuronal function. Indeed, hyperphosphorylation of tau closely contributes to neuronal dysfunction leading to neurodegenerative diseases, including tauopathies, which are characterized by excessive and aberrant tau phosphorylation and cognitive decline. Therefore, it is important to understand how to regulate its phosphorylation. In this regard, the protein tyrosine phosphatase receptor delta (PTPRD) has been genetically implicated in tau pathology in humans, but the mechanisms underlying its role in tau regulation remain unclear. This study investigates the impact of Ptprd deficiency on tau phosphorylation, cognitive function, neuroinflammation, and synaptic markers in aging mice. Results Mice lacking Ptprd showed increased tau phosphorylation at multiple sites associated with its pathological aggregation. This effect was accompanied by the activation of the tau-related kinase Abl1, particularly in the hippocampus. Behavioral assessments revealed significant impairments in learning and memory, demonstrating the functional impact of these alterations. Moreover, Ptprd knockout mice showed increased microgliosis in both the entorhinal cortex and the hippocampus, suggesting a pro-inflammatory response. Furthermore, the synaptic protein PSD95 was also reduced in the cortex, indicating potential synaptic dysfunction. Conclusions The loss of Ptprd leads to increased tau phosphorylation, cognitive impairments, microgliosis, and synaptic alterations in older mice. Our findings also suggest that Ptprd plays a critical role in maintaining tau homeostasis through the Abl1 kinase. This indicates a new potential therapeutic approach for tauopathies, where PTPRD could serve a protective role against tau-related pathologies and may act as a key modulator in disease progression.