TIME COURSE OF CHANGES OF FOSB IMMUNOREACTIVITY IN NUCLEUS OF SOLITARY TRACT DURING CHRONIC INTERMITTENT HYPOXIA
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Abstract
Purpose: To determine the time course of the onset of FosB expression during 7 days of exposure to chronic intermittent hypoxia (CIH), a widely used model of the arterial hypoxemia that occurs during sleep apnea. FosB is a member of the transcription factor Activator Protein-1 (AP-1) family. FosB is not constitutively expressed in the central nervous system (CNS) and is induced following chronic stimulation. A previous study from our group found that the number of FosB immunoreactive neurons in the nucleus of solitary tract (NTS) is increased after 7 days of exposure to CIH (alternating 3min periods of 10% O2 with 3min 21% O2 from 8am-4pm). Methods: We measured the number of FosB immunoreactive neurons in male Sprague Dawley rats exposed to either room air (control) or to CIH. On the day following exposure to CIH for 1 day, 3 days, 5 days or 7 days (n= 6 for each CIH group and 14 for control group), rats were perfused with paraformaldehyde and brains processed for FosB immunohistochemistry using an antibody (Santa Cruz) that does not distinguish FosB from ΔFosB. Results: The number of FosB immunoreactive neurons in caudal NTS in the control group was 11± 2 cells/section (c/s). After 1 day CIH the number of FosB immunoreactive neurons increased to 40± 11 c/s, 3 days CIH 35±8 c/s, 5 days CIH 36±5 c/s and 7 days CIH 29±4 c/s. The differences between the control group and the CIH groups were significant. Three days after 7 days exposure to CIH the number of FosB immunoreactive neurons in NTS had returned to 10 ± 3 c/s (n=2). Conclusions: This study indicates that FosB expression develops rapidly during exposure to CIH and remains elevated during a 7 day exposure.