6 results
Search Results
Now showing 1 - 6 of 6
Item Rosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Mice(2023-05-06) Lobos, Nicolás; Lux, Sebastián; Zepeda, Ramiro Javier; Pelissier, Teresa; Marcos, José Luis; Bustos-Quevedo, Gonzalo; Hernández, Alejandro; Constandil, LuisPaclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED30, von Frey testing) and thermal hyperalgesia (ED50, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED30 and ED50 for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.Item Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity(2022-09-20) Olivares-Barraza, Rossy; Marcos, José Luis; Martínez-Pinto, Jonathan; Fuenzalida, Marco; Bravo, Javier A.; Gysling, Katia; Sotomayor-Zárate, RamónObesity is a pandemic associated with lifestyles changes. These include excess intake of obesogenic foods and decreased physical activity. Brain areas, like the lateral hypothalamus (LH), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been linked in both homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. Interestingly, these control systems are regulated by the lateral septum (LS), a relay of γ-aminobutyric (GABA) acid neurons (GABAergic neurons) that inhibit the LH and GABAergic interneurons of the VTA. Furthermore, the LS has a diverse receptor population for neurotransmitters and neuropeptides such as dopamine, glutamate, GABA and corticotropin-releasing factor (CRF), among others. Particularly, CRF a key player in the stress response, has been related to the development of overweight and obesity. Moreover, evidence shows that LS neurons neurophysiologically regulate reward and stress, although there is little evidence of LS taking part in homeostatic and hedonic feeding. In this review, we discuss the evidence that supports the role of LS and CRF on feeding, and how alterations in this system contribute to weight gain obesity.Item Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake(2023-01-11) Marcos, José Luis; Olivares-Barraza, Rossy; Ceballo, Karina; Wastavino, Melisa; Ortiz, Víctor; Riquelme, Julio; Martínez-Pinto, Jonathan; Muñoz, Pablo; Cruz, Gonzalo; Sotomayor-Zárate, RamónObesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.Item Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity(2022-09-20) Olivares-Barraza, Rossy; Marcos, José Luis; Martínez-Pinto, Jonathan; Fuenzalida, Marco; Bravo, Javier A.; Gysling, Katia; Sotomayor-Zárate, RamónObesity is a pandemic associated with lifestyles changes. These include excess intake of obesogenic foods and decreased physical activity. Brain areas, like the lateral hypothalamus (LH), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been linked in both homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. Interestingly, these control systems are regulated by the lateral septum (LS), a relay of γ-aminobutyric (GABA) acid neurons (GABAergic neurons) that inhibit the LH and GABAergic interneurons of the VTA. Furthermore, the LS has a diverse receptor population for neurotransmitters and neuropeptides such as dopamine, glutamate, GABA and corticotropin-releasing factor (CRF), among others. Particularly, CRF a key player in the stress response, has been related to the development of overweight and obesity. Moreover, evidence shows that LS neurons neurophysiologically regulate reward and stress, although there is little evidence of LS taking part in homeostatic and hedonic feeding. In this review, we discuss the evidence that supports the role of LS and CRF on feeding, and how alterations in this system contribute to weight gain obesity.Item Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake(2023-01-11) Marcos, José Luis; Olivares-Barraza, Rossy; Ceballo, Karina; Wastavino, Melisa; Ortiz, Víctor; Riquelme, Julio; Martínez-Pinto, Jonathan; Muñoz, Pablo; Cruz, Gonzalo; Sotomayor-Zárate, RamónObesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.Item DETECCIÓN DE Trypanosoma cruzi EN LAGARTOS Microlophus atacamensis DE UNA ISLA COSTERA DEL DESIERTO DE ATACAMA(2024-06) Borcosque. Josefa; Campos-Soto, Ricardo; Quiroga, Nicol; Cianferoni, Franco; Díaz-Campusano, Gabriel; Marcos, José Luis; Botto-Mahan, Carezza; Torres-Pérez, FernandoLa enfermedad de Chagas es producida por el parásito Trypanosoma cruzi, el cual está presente en vinchucas y sangre/tejidos de mamíferos, considerándose las aves refractarias a la infección. Mepraia es un género de vinchuca responsable de transmitir T. cruzi en el ciclo silvestre de Chile. Se ha evidenciado la presencia de ejemplares de Mepraia infectados con T. cruzi en la Isla Santa María (Región de Antofagasta). En esta isla no se ha registrado presencia de micromamíferos y los vertebrados más comunes son el lagarto Microlophus atacamensis, jotes y aves marinas. En las vinchucas de esta isla se ha reportado un alto porcentaje de infección e incluso infecciones mixtas, con más de un DTU de T. cruzi, lo que está comúnmente asociado a ecosistemas con una alta biodiversidad y abundancia de mamíferos. Esto contrasta con la nula captura de micromamíferos reportada en esta isla. Considerando que recientemente se ha publicado que los reptiles también son hospederos de T. cruzi, se puede inferir que los lagartos M. atacamensis podrían estar manteniendo la infección de T. cruzi en la Isla Santa María. El objetivo de este estudio es determinar si individuos de M. atacamensis de la Isla Santa María son hospederos de T. cruzi. En 33 muestras de sangre de M. atacamensis se detectó T. cruzi mediante la amplificación de un segmento de ADN kinetoplastídico por PCR convencional y un segmento nuclear de T. cruzi por real time PCR. Se determinó un 60.6% de infección mediante PCR convencional, mientras que por real time PCR un 51.1%. Se concluye que M. atacamensis es un hospedero de T. cruzi, sugiriendo que podría ser un reservorio clave que está mantenido la infección en la Isla Santa María. Estos resultados contribuyen al entendimiento del ciclo de vida que desarrolla T. cruzi en esta particular isla del extremo norte del desierto de Atacama.