Browsing by Author "von Bernhardi, Rommy"

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    Phosphorylated tau potentiates Aβ-induced mitochondrial damage in mature neurons
    (2014) Quintanilla, Rodrigo A.; von Bernhardi, Rommy; Godoy, Juan A.; Inestrosa, Nibaldo C.; Johnson, Gail V. W.
    Tau phosphorylated at the PHF-1 epitope (S396/S404) is likely involved in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which tau phosphorylated at these sites negatively impacts neuronal functions are still under scrutiny. Previously, we showed that expression of tau truncated at D421 enhances mitochondrial dysfunction induced by A beta in cortical neurons. To extend these findings, we expressed tau pseudo-phosphorylated at S396/404 (T42EC) in mature and young cortical neurons and evaluated different aspects of mitochondrial function in response to A beta. Expression of T42EC did not induce significant changes in mitochondrial morphology, mitochondrial length, or mitochondrial transport, compared to GFP and full-length tau. However, T42EC expression enhanced A beta-induced mitochondrial membrane potential loss and increased superoxide levels compared to what was observed in mature neurons expressing full-length tau. The same effect was observed in mature neurons that expressed both pseudo-phosphorylated and truncated tau when they were treated with AS. Interestingly, the mitochondrial failure induced by A beta in mature neurons that expressed T42EC, was not observed in young neurons expressing T42EC. These novel findings suggest that phosphorylated tau (PHF-1 epitope) enhances A beta-induced mitochondrial injury, which contributes to neuronal dysfunction and to the pathogenesis of AD. (C) 2014 Elsevier Inc All rights reserved.
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    Prenatal to Early Postnatal Nicotine Exposure Impairs Central Chemoreception and Modifies Breathing Pattern in Mouse Neonates: A Probable Link to Sudden Infant Death Syndrome
    (SOC NEUROSCIENCE, 2008) Eugenin, Jaime; Otarola, Marcelo; Bravo, Eduardo; Coddou, Claudio; Cerpa, Veronica; Reyes Parada, Miguel; Llona, Isabel; von Bernhardi, Rommy
    Nicotine is a neuroteratogen and is the likely link between maternal cigarette smoking during pregnancy and sudden infant death syndrome (SIDS). Osmotic minipumps were implanted in 5-7 d CF1 pregnant mice to deliver nicotine bitartrate (60 mg Kg(-1) day(-1)) or saline (control) solutions for up to 28 d. Prenatal to early postnatal nicotine exposure did not modify the number of newborns per litter or their postnatal growth; however, nicotine-exposed neonates hypoventilated and had reduced responses to hypercarbia (inhalation of air enriched with 10% CO2 for 20 min) and hypoxia (inhalation of 100% N-2 for 20 s) at postnatal days 0-3 (P0-P3). In contrast, at postnatal day 8, nicotine-exposed neonates were indistinguishable from controls. Isolated brainstem-spinal cord preparations obtained from P0 to P3 nicotine-exposed neonates showed fictive respiration with respiratory cycles longer and more irregular than those of controls, as indicated by high short- and long-term variability in Poincare plots. In addition, their responses to acidification were reduced, indicating compromise of central chemoreception. Furthermore, the cholinergic contribution to central chemosensory responses switched from muscarinic receptor to nicotinic receptor-based mechanisms. No significant astrogliosis was detectable in the ventral respiratory group of neurons with glial fibrillary acidic protein immunohistochemistry. These results indicate that nicotine exposure affects the respiratory rhythm pattern generator and causes a decline in central chemoreception during early postnatal life. Consequently, breathing would become highly vulnerable, failing to respond to chemosensory demands. Such impairment could be related to the ventilatory abnormalities observed in SIDS.
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    The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases
    (2021) Jose Trivino, Juan; von Bernhardi, Rommy
    Microglia serve key functions in the central nervous system (CNS), participating in the establishment and regulation of synapses and the neuronal network, and regulating activity-dependent plastic changes. As the neuroimmune system, they respond to endogenous and exogenous signals to protect the CNS. In aging, one of the main changes is the establishment of inflamm-aging, a mild chronic inflammation that reduces microglial response to stressors. Neuroinflammation depends mainly on the increased activation of microglia. Microglia over-activation may result in a reduced capacity for performing normal functions related to migration, clearance, and the adoption of an anti-inflammatory state, contributing to an increased susceptibility for neurodegeneration. Oxidative stress contributes both to aging and to the progression of neurodegenerative diseases. Increased production of reactive oxygen species (ROS) and neuroinflammation associated with age-and disease dependent mechanisms affect synaptic activity and neurotransmission, leading to cognitive dysfunction. Astrocytes prevent microglial cell cytotoxicity by mechanisms mediated by transforming growth factor 131 (TGF131). However, TGF131-Smad3 pathway is impaired in aging, and the age-related impairment of TGF13 signaling can reduce protective activation while facilitating cytotoxic activation of microglia. A critical analysis on the effect of aging microglia on neuronal function is relevant for the understanding of age-related changes on neuronal function. Here, we present evidence in the context of the ?microglial dysregulation hypothesis?, which leads to the reduction of the protective functions and increased cytotoxicity of microglia, to discuss the mechanisms involved in neurodegenerative changes and Alzheimer?s disease.