Browsing by Author "Lindsay, Carolina B."
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- ItemAndrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3 beta : autoregulation of GSK-3 beta in vivo(2015) Tapia Rojas, Cheril Cecilia; Schüller, Andreas; Lindsay, Carolina B.; Ureta, Roxana C.; Melo Ledermann, Francisco Javier; Mejías Reyes, Cristóbal; Hancke, Juan; Inestrosa Cantín, Nibaldo
- ItemAndrographolide Reduces Neuroinflammation and Oxidative Stress in Aged Octodon degus(SPRINGER, 2020) Lindsay, Carolina B.; Zolezzi, Juan M.; Rivera, Daniela S.; Cisternas, Pedro; Bozinovic, Francisco; Inestrosa, Nibaldo C.Alzheimer's disease (AD) is a devastating neurodegenerative disorder in which superior brain functions, such as memory and cognition, are impaired. Currently, no effective treatment is available for AD. Although andrographolide (ANDRO), a compound extracted from the herb Andrographis paniculata, has shown interesting effects in models of several diseases, including AD, its effects on other molecular changes observed in AD, such as neuroinflammation and oxidative stress, have not yet been studied. To evaluate the impact of ANDRO-based intervention on the levels of amyloid-beta (A beta) and neuroinflammatory and oxidative stress markers in the brains of aged Octodon degus, a Chilean rodent, fifty-six-month-old O. degus were treated intraperitoneally with 2 or 4 mg/kg ANDRO. Vehicle-injected and 12-month-old O. degus were used as positive controls. Then, the protein levels of selected markers were assessed via immunohistochemistry and immunoblotting. ANDRO significantly reduced the total A beta burden as well as astrogliosis and interleukin-6 levels. Moreover, ANDRO significantly reduced the levels of 4-hydroxynonenal and N-tyrosine adducts, suggesting a relevant reduction in oxidative stress within aged O. degus brain. Considering that O. degus has been proposed as a potential "natural" model for sporadic AD due to the development of neuropathological markers that resemble this pathology, our results suggest that ANDRO should be further studied to establish its potential as a therapeutic drug for AD.
- ItemIs L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice(2015) Tapia Rojas, Cheril Cecilia; Lindsay, Carolina B.; Montecinos Oliva, Carla; Arrazola Tello, Macarena Soledad.; Retamales, Rocio M.; Inestrosa Cantín, Nibaldo; Bunout, Daniel; Hirsch, Sandra.Abstract Background L-methionine, the principal sulfur-containing amino acid in proteins, plays critical roles in cell physiology as an antioxidant and in the breakdown of fats and heavy metals. Previous studies suggesting the use of L-methionine as a treatment for depression and other diseases indicate that it might also improve memory and propose a role in brain function. However, some evidence indicates that an excess of methionine can be harmful and can increase the risk of developing Type-2 diabetes, heart diseases, certain types of cancer, brain alterations such as schizophrenia, and memory impairment. Results Here, we report the effects of an L-methionine-enriched diet in wild-type mice and emphasize changes in brain structure and function. The animals in our studypresented 1) higher levels of phosphorylated tau protein, 2) increased levels of amyloid-β (Aβ)-peptides, including the formation of Aβ oligomers, 3) increased levels of inflammatory response,4) increased oxidative stress, 5) decreased level of synaptic proteins, and 6) memory impairment and loss. We also observed dysfunction of the Wnt signaling pathway. Conclusion Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer’s-like neurodegeneration.
- ItemLong-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in Octodon degus(2018) Rivera, Daniela S.; Lindsay, Carolina B.; Codocedo Henríquez, Juan Francisco; Carreño, Laura E.; Cabrera, Daniel; Arrese Jiménez, Marco; Vio Lagos, Carlos P.; Bozinovic Kuscevic, Francisco; Inestrosa Cantín, Nibaldo
- ItemQuercetin Exerts Differential Neuroprotective Effects Against H2O2 and A beta Aggregates in Hippocampal Neurons: the Role of Mitochondria(2017) Godoy, Juan A.; Lindsay, Carolina B.; Quintanilla, Rodrigo A.; Carvajal Cachaña, Francisco Javier; Cerpa Nebott, Waldo Francisco; Inestrosa Cantín, Nibaldo
- ItemThe 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