Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia, and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg, i.p. daily) or saline beginning one day before and during 7 days of chronic hypoxia (CH, PIO2 = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly (p < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 minutes to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 hour of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 hours of CH. Astrocytes increased GFAP antibody immunofluorescent intensity, indicating activation, at both 4 and 24 hours of CH. Minocycline had no effect on glia in normoxia, but significantly decreased microglia activation at 1 hour of CH and astrocyte activation at 24 hours of CH. These results support a role for glial cells providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia.
- hypoxic ventilatory response
- nucleus tractus solitarius
- neural plasticity
- Copyright © 2016, Journal of Neurophysiology