Browsing by Author "Salazar, Paulina"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis
    (2016) Cisternas, Pedro; Salazar, Paulina; Silva Alvarez, Carmen; Barros, L. Felipe; Inestrosa Cantín, Nibaldo
  • No Thumbnail Available
    Item
    Adiponectin and resistin modulate the progression of Alzheimer's disease in a metabolic syndrome model
    (2023) Cisternas, Pedro; Gherardelli, Camila; Gutierrez, Joel; Salazar, Paulina; Mendez-Orellana, Carolina; Wong, G. William; Inestrosa, Nibaldo C.
    Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related brain diseases, including Alzheimer's disease (AD). However, the underlying mechanism explaining the link between MetS and brain function is poorly understood. Among the possible mediators are several adipose-derived secreted molecules called adipokines, including adiponectin (ApN) and resistin, which have been shown to regulate brain function by modulating several metabolic processes. To investigate the impact of adipokines on MetS, we employed a diet-induced model to induce the various complications associated with MetS. For this purpose, we administered a high-fat diet (HFD) to both WT and APP/PSN1 mice at a pre-symptomatic disease stage. Our data showed that MetS causes a fast decline in cognitive performance and stimulates A beta(42) production in the brain. Interestingly, ApN treatment restored glucose metabolism and improved cognitive functions by 50% while decreasing the A beta(42/40) ratio by approximately 65%. In contrast, resistin exacerbated Ab pathology, increased oxidative stress, and strongly reduced glucose metabolism. Together, our data demonstrate that ApN and resistin alterations could further contribute to AD pathology.
  • No Thumbnail Available
    Item
    Disruption of Glucose Metabolism in Aged Octodon degus: A Sporadic Model of Alzheimer's Disease
    (2021) Cisternas, Pedro; Gherardelli, Camila; Salazar, Paulina; Inestrosa, Nibaldo C.
    Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia. Although transgenic Alzheimer's disease (AD) animal models have greatly contributed to our understanding of the disease, therapies tested in these animals have resulted in a high rate of failure in preclinical trials for AD. A promising model is Octodon degus (degu), a Chilean rodent that spontaneously develops AD-like neuropathology. Previous studies have reported that, during aging, degus exhibit a progressive decline in cognitive function, reduced neuroinflammation, and concomitant increases in the number and size of amyloid beta (A beta) plaques in several brain regions. Importantly, in humans and several AD models, a correlation has been shown between brain dysfunction and neuronal glucose utilization impairment, a critical aspect considering the high-energy demand of the brain. However, whether degus develop alterations in glucose metabolism remains unknown. In the present work, we measured several markers of glucose metabolism, namely, glucose uptake, ATP production, and glycolysis and pentose phosphate pathway (PPP) flux, in hippocampal slices from degus of different ages. We found a significant decrease in hippocampal glucose metabolism in aged degus, caused mainly by a drop in glucose uptake, which in turn, reduced ATP synthesis. Moreover, we observed a negative correlation between age and PPP flux. Together, our data further support the use of degus as a model for studying the neuropathology involved in sporadic AD-like pathology and as a potentially valuable tool in the search for effective treatments against the disease.
  • Thumbnail Image
    Item
    Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance
    (2015) Cisternas, Pedro; Salazar, Paulina; Serrano, Felipe G.; Montecinos Oliva, Carla; Arredondo, Sebastián B.; Varela Nallar, Lorena Patricia; Barja Y., Salesa; Vio Lagos, Carlos P.; Gomez Pinilla, Fernando; Inestrosa Cantín, Nibaldo
  • Thumbnail Image
    Item
    The increased potassium intake improves cognitive performance and attenuates histopathological markers in a model of Alzheimer's disease
    (2015) Cisternas, Pedro; Lindsay, Carolina B.; Salazar, Paulina; Silva Álvarez, Carmen; Retamales, Rocio M.; Serrano, Felipe G.; Vio Lagos, Carlos P.; Inestrosa Cantín, Nibaldo