Browsing by Author "Ramirez, Gigliola"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Exercise training reduces brainstem oxidative stress and restores normal breathing function in heart failure
    (2021) Diaz-Jara, Esteban; Diaz, Hugo S.; Rios-Gallardo, Angelica; Ortolani, Domiziana; Andrade, David C.; Toledo, Camilo; V. Pereyra, Katherin; Schwarz, Karla; Ramirez, Gigliola; Ortiz, Fernando C.; Andia, Marcelo E.; Del Rio, Rodrigo
    Enhanced central chemoreflex drive and irregular breathing are both hallmarks in heart failure (HF) and closely related to disease progression. Central chemoreceptor neurons located within the retrotrapezoid nucleus (RTN) are known to play a role in breathing alterations in HF. It has been shown that exercise (EX) effectively reduced reactive oxygen species (ROS) in HF rats. However, the link between EX and ROS, particularly at the RTN, with breathing alterations in HF has not been previously addressed. Accordingly, we aimed to determine: i) ROS levels in the RTN in HF and its association with chemoreflex drive, ii) whether EX improves chemoreflex/breathing function by reducing ROS levels, and iii) determine molecular alterations associated with ROS generation within the RTN of HF rats and study EX effects on these pathways. Adult male Sprague-Dawley rats were allocated into 3 experimental groups: Sham (n = 5), volume overloaded HF (n = 6) and HF (n = 8) rats that underwent EX training for 6 weeks (60 min/day, 25 m/min, 10% inclination). At 8 weeks post-HF induction, breathing patterns and chemoreflex function were analyzed by unrestrained plethysmography. ROS levels and anti/pro-oxidant enzymes gene expression were analyzed in the RTN. Our results showed that HF rats have high ROS levels in the RTN which were closely linked to the enhanced central chemoreflex and breathing disorders. Also, HF rats displayed decreased expression of antioxidant genes in the RTN compared with control rats. EX training increases antioxidant defense in the RTN, reduces ROS formation and restores normal central chemoreflex drive and breathing regularity in HF rats. This study provides evidence for a role of ROS in central chemoreception in the setting of HF and support the use of EX to reduce ROS in the brainstem of HF animals and reveal its potential as an effective mean to normalize chemoreflex and breathing function in HF.
  • Thumbnail Image
    Item
    Mucosal Exposure to Cigarette Components Induces Intestinal Inflammation and Alters Antimicrobial Response in Mice
    (2019) Berkowitz Fiebich, Loni; Pardo Roa, Catalina; Salazar, Geraldine A.; Salazar Echegarai, Francisco Javier; Miranda Marín, José Patricio; Ramirez, Gigliola; Chávez, José L.; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan; Alvarez Lobos, M.
  • No Thumbnail Available
    Item
    Proinflammatory stimuli are needed for induction of microglial cell-mediated A beta PP244-C and A beta-neurotoxicity in hippocampal cultures
    (IOS PRESS, 2008) Ramirez, Gigliola; Rey, Sergio; von Bernhardi, Rommy
    Amyloid-beta plaques and neurodegeneration are hallmarks of Alzheimer's disease, where glial cells are responsible for sustained neuroinflammation. Here we show that hippocampal-microglia co-cultures exposed to proinflammatory mediators, amyloid-beta- and amyloid-beta protein precursor construct-conjugated beads increased their production of nitrites. In contrast, inflammation was unable to significantly induce cell death by itself, whereas inflammation plus amyloid-beta or amyloid-beta protein precursor induced a significant increment of cell death and a 6-fold increase of production of Interleukin 1 beta. Those effects were not observed in the absence of microglia or when hippocampal cells were co-cultured with microglia for one day. In contrast, a 2-fold increase of transforming growth factor beta 1 was observed in hippocampal cultures exposed to inflammatory stimuli for 4 days, whereas induction of transforming growth factor beta 1 by inflammation plus amyloid-beta and amyloid-beta protein precursor was nearly abolished by microglia. Our results indicate that neurotoxicity induced by amyloid-beta or amyloid-beta protein precursor was a slow process depending on activated microglia and additional stimuli. The observed cytotoxicity could be consequence of a vicious cycle in which elevated concentrations of Interleukin 1 beta and radical species along with decreased secretion of neuroprotective cytokines such as transforming growth factor beta 1 support persistent activation of glial cells and cell damage.