Reduced c-Fos expression in medullary catecholaminergic neurons in rats 20 h after exposure to chronic intermittent hypoxia

Abstract

Persons affected by obstructive sleep apnea (OSA) have increased arterial blood pressure and elevated activity in upper airway muscles. Many cardiorespiratory features of OSA have been reproduced in rodents subjected to chronic-intermittent hypoxia (CIH). We previously reported that, following exposure to CIH, rats have increased noradrenergic terminal density in brain stem sensory and motor nuclei and upregulated expression of the excitatory α(1)-adrenergic receptors in the hypoglossal motor nucleus. This suggested that CIH may enhance central catecholaminergic transmission. We now quantified c-Fos expression in different groups of pontomedullary catecholaminergic neurons as an indirect way of assessing their baseline activity in rats subjected to CIH or sham treatment (7 AM-5 PM daily for 35 days). One day after the last CIH exposure, the rats were gently kept awake for 2.5 h and then were anesthetized and perfused, and their pontomedullary brain sections were subjected to dopamine β-hydroxylase (DBH) and c-Fos immunohistochemistry. DBH-positive cells were counted in the A1/C1, A2/C2, A5, subcoeruleus (sub-C) and A7 groups of catecholaminergic neurons, and the percentages of those expressing c-Fos were determined. We found that fewer DBH cells expressed c-Fos in CIH- than in sham-treated rats in the medulla (significant in the A1 group). In the pons (rostral A5, sub-C, and A7), c-Fos expression did not differ between the CIH- and sham-treated animals. We suggest that, when measured 20 h after the last CIH exposure, catecholaminergic transmission is enhanced through terminal sprouting and receptor upregulation rather than through increased baseline activity in pontomedullary catecholaminergic neurons.

Transcription factors regulate GPR91-mediated expression of VEGF in hypoxia-induced retinopathy

“…The upregulation of C/EBP β and c-Fos activity and function in hypoxic states is potentially problematic for the retina. However, Herr KB et al 35. reported that chronic intermittent hypoxia reduced the baseline activity of c-Fos in medullary catecholaminergic neurons.…”

Sleep-disordered breathing: Effects on brain structure and function

“…Adrenergic neurons in the subcoeruleus and neighboring areas play roles in upper airway muscle responses to intermittent hypoxia (Herr et al, 2013). …”

Chick embryos have the same pattern of hypoxic lower‐brain activation as fetal mammals

“…Slides from all three conditions were stained at the same time, and quantification of cFos labeling was performed blindly with respect to the origin of the slides. cFos is induced by the activation of multiple signal transduction pathways (Hoffman and Lyo, 2002;Hassani et al, 2009), and changes in its expression have been related to differences in neuronal activity in particular cell populations (Hoffman and Lyo, 2002;Benincasa Herr et al, 2013). Although cFos induction is not a straightforward marker of increased neuronal firing rates, it does indicate the onset of activityrelated changes in neuronal metabolism or morphology that require changes in gene expression (Cirelli and Tononi, 2000;Benincasa Herr et al, 2013).…”

“…cFos is better considered as a marker of metabolic/structural changes that require changes in gene expression (Cirelli and Tononi, 2000), induced in response to combinations of input events. Even though cFos is not a direct read-out of generalized cell electrical activity, it has been (and is still being) used to successfully map specific neural circuitry involved in brain responses to hypoxia in both adult (Berquin et al, 2000;King et al, 2012;Benincasa Herr et al, 2013) and fetal mammals (Breen et al, 1997;Nitsos and Walker, 1999b). cFos thus provides one of the few ways to simultaneously survey the responses of large populations of neurons with single-cell resolution in embryos (Hoffman and Lyo, 2002).…”