Browsing by Author "Inostroza, Carla A."

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    Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders
    (2021) Prieto Villalobos, Juan Carlos; Alvear Soto, Tanhia Francheska; Liberona, Andres; Lucero, Claudia M.; Martinez Araya, Claudio J.; Balmazabal, Javiera; Inostroza, Carla A.; Ramírez Rojas, Gigliola; Gomez, Gonzalo I.; Orellana Roca, Juan Andrés
    Maternal inflammation during pregnancy causes later-in-life alterations of the offspring's brain structure and function. These abnormalities increase the risk of developing several psychiatric and neurological disorders, including schizophrenia, intellectual disability, bipolar disorder, autism spectrum disorder, microcephaly, and cerebral palsy. Here, we discuss how astrocytes might contribute to postnatal brain dysfunction following maternal inflammation, focusing on the signaling mediated by two families of plasma membrane channels: hemi-channels and pannexons. [Ca2+](i) imbalance linked to the opening of astrocytic hemichannels and pannexons could disturb essential functions that sustain astrocytic survival and astrocyte-to-neuron support, including energy and redox homeostasis, uptake of K+ and glutamate, and the delivery of neurotrophic factors and energy-rich metabolites. Both phenomena could make neurons more susceptible to the harmful effect of prenatal inflammation and the experience of a second immune challenge during adulthood. On the other hand, maternal inflammation could cause excitotoxicity by producing the release of high amounts of gliotransmitters via astrocytic hemichannels/pannexons, eliciting further neuronal damage. Understanding how hemichannels and pannexons participate in maternal inflammation-induced brain abnormalities could be critical for developing pharmacological therapies against neurological disorders observed in the offspring.
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    Connexin 43 hemichannels and pannexin-1 channels contribute to the alpha-synuclein-induced dysfunction and death of astrocytes
    (2019) Díaz Jara, Esteban Fernando; Labra Ramírez, Valeria Cristina; Alvear, Tanhia F.; Mellado, Luis A.; Inostroza, Carla A.; Oyarzún Isamitt, Juan Esteban; Salgado Cortés, Nicole Andrea; Quintanilla Gómez, Rodrigo Arthur; Orellana Roca, Juan Andrés
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    The Opening of Connexin 43 Hemichannels Alters Hippocampal Astrocyte Function and Neuronal Survival in Prenatally LPS-Exposed Adult Offspring
    (2019) Chávez Chaname, Carolina Elizabeth; Oyarzún Isamitt, Juan Esteban; Avendaño, Beatriz C.; Mellado, Luis A.; Inostroza, Carla A.; Alvear Soto, Tanhia Francheska; Orellana Roca, Juan Andrés
    Clinical evidence has revealed that children born from mothers exposed to viral and bacterial pathogens during pregnancy are more likely to suffer various neurological disorders including schizophrenia, autism bipolar disorder, major depression, epilepsy, and cerebral palsy. Despite that most research has centered on the impact of prenatal inflammation in neurons and microglia, the potential modifications of astrocytes and neuron-astrocyte communication have received less scrutiny. Here, we evaluated whether prenatally LPS-exposed offspring display alterations in the opening of astrocyte hemichannels and pannexons in the hippocampus, together with changes in neuroinflammation, intracellular Ca2+ and nitric oxide (NO) signaling, gliotransmitter release, cell arborization, and neuronal survival. Ethidium uptake recordings revealed that prenatal LPS exposure enhances the opening of astrocyte Cx43 hemichannels and Panx1 channels in the hippocampus of adult offspring mice. This enhanced channel activity occurred by a mechanism involving a microglia-dependent production of IL-1 beta/TNF-alpha and the stimulation of p38 MAP kinase/iNOS/[Ca2+](i)-mediated signaling and purinergic/glutamatergic pathways. Noteworthy, the activity of Cx43 hemichannels affected the release of glutamate, [Ca2+](i) handling, and morphology of astrocytes, whereas also disturbed neuronal function, including the dendritic arbor and spine density, as well as survival. We speculate that excitotoxic levels of glutamate triggered by the activation of Cx43 hemichannels may contribute to hippocampal neurotoxicity and damage in prenatally LPS-exposed offspring. Therefore, the understanding of how astrocyte-neuron crosstalk is an auspicious avenue toward the development of broad treatments for several neurological disorders observed in children born to women who had a severe infection during gestation.