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Wilkinson K.A.,University of California at San Diego | Fu Z.,University of California at San Diego | Powell F.L.,University of California at San Diego | Powell F.L.,White Mountain Research Center
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2011

During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower PCO 2 levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO 2- sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired PO 2 = 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH. © 2011 the American Physiological Society.

Popa D.,University of California at San Diego | Fu Z.,University of California at San Diego | Fu Z.,White Mountain Research Center | Go A.,University of California at San Diego | And 2 more authors.
Respiratory Physiology and Neurobiology | Year: 2011

Recently, inflammatory processes have been shown to increase O 2-sensitivity of the carotid body during chronic sustained hypoxia [Liu, X., He, L., Stensaas, L., Dinger, B., Fidone, S., 2009. Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. Am. J. Physiol. Lung Cell Mol. Physiol. 296, L158-L166]. We hypothesized that blocking inflammation with ibuprofen would reduce ventilatory acclimatization to hypoxia by blocking such increases in carotid body O 2 sensitivity. We tested this in conscious rats treated with ibuprofen (4mg/kg IP daily) or saline during acclimatization to hypoxia (PIO2=70 Torr for 7 days). Ibuprofen blocked the increase in hypoxic ventilation observed in chronically hypoxic rats treated with saline; ibuprofen had no effects on ventilation in normoxic control rats. Ibuprofen blocked increases in inflammatory cytokines (IL-1β, IL-6) in the brainstem with chronic hypoxia. The data supports our hypothesis and further analysis indicates that ibuprofen also blocks inflammatory processes in the central nervous system contributing to ventilatory acclimatization to hypoxia. Possible mechanisms linking inflammatory and hypoxic signaling are reviewed. © 2011 Elsevier B.V.

Boychuk E.C.,University of Western Ontario | Boychuk E.C.,White Mountain Research Center | Smiley J.T.,White Mountain Research Center | Dahlhoff E.P.,White Mountain Research Center | And 5 more authors.
Journal of Insect Physiology | Year: 2015

Small ectothermic animals living at high altitude in temperate latitudes are vulnerable to lethal cold throughout the year. Here we investigated the cold tolerance of the leaf beetle Chrysomela aeneicollis living at high elevation in California's Sierra Nevada mountains. These insects spend over half their life cycle overwintering, and may therefore be vulnerable to winter cold, and prior studies have demonstrated that survival is reduced by exposure to summertime cold. We identify overwintering microhabitat of this insect, describe cold tolerance strategies in all life stages, and use microclimate data to determine the importance of snow cover and microhabitat buffering for overwinter survival. Cold tolerance varies among life history stages and is typically correlated with microhabitat temperature: cold hardiness is lowest in chill-susceptible larvae, and highest in freeze-tolerant adults. Hemolymph osmolality is higher in quiescent (overwintering) than summer adults, primarily, but not exclusively, due to elevated hemolymph glycerol. In nature, adult beetles overwinter primarily in leaf litter and suffer high mortality if early, unseasonable cold prevents them from entering this refuge. These data suggest that cold tolerance is tightly linked to life stage. Thus, population persistence of montane insects may become problematic as climate becomes more unpredictable and climate change uncouples the phenology of cold tolerance and development from the timing of extreme cold events. © 2015 Elsevier Ltd.

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