Abstract
Due to phoenixin’s role in restraint stress and glucocorticoid stress, as well as its recently shown effects on the inflammasome, we aimed to investigate the effects of lipopolysaccharide (LPS)-induced inflammatory stress on the activity of brain nuclei-expressing phoenixin. Male Sprague Dawley rats (n = 6/group) were intraperitoneally injected with either LPS or control (saline). Brains were processed for c-Fos and phoenixin immunohistochemistry and the resulting slides were evaluated using ImageJ software. c-Fos was counted and phoenixin was evaluated using densitometry. LPS stress significantly increased c-Fos expression in the central amygdaloid nucleus (CeM, 7.2-fold), supraoptic nucleus (SON, 34.8 ± 17.3 vs. 0.0 ± 0.0), arcuate nucleus (Arc, 4.9-fold), raphe pallidus (RPa, 5.1-fold), bed nucleus of the stria terminalis (BSt, 5.9-fold), dorsal motor nucleus of the vagus nerve (DMN, 89-fold), and medial part of the nucleus of the solitary tract (mNTS, 121-fold) compared to the control-injected group (p < 0.05). Phoenixin expression also significantly increased in the CeM (1.2-fold), SON (1.5-fold), RPa (1.3-fold), DMN (1.3-fold), and mNTS (1.9-fold, p < 0.05), leading to a positive correlation between c-Fos and phoenixin in the RPa, BSt, and mNTS (p < 0.05). In conclusion, LPS stress induces a significant increase in activity in phoenixin immunoreactive brain nuclei that is distinctively different from restraint stress.
Highlights
In recent years, interest in phoenixin, with its 14 and 20 amino acid sequences, has continuously increased and its functions in basic physiological processes have become more and more apparent
LPS injection induced a significant increase in the number of c-Fos-positive neurons in the CeM (4.83 ± 0.96 vs. 0.67 ± 0.17; p < 0.001; Figure 2A), supraoptic nucleus (SON) (37.5 ± 2.75 vs. 0.0 ± 0.0; p < 0.001; Figure 3A), Arc (18.24 ± 1.75 vs. 3.7 ± 0.79; p < 0.001; Figure 4A), RPa (11.7 ± 1.47 vs. 2.27 ± 0.57; p < 0.001; Figure 5A), BSt (8.27 ± 1.74 vs. 1.37 ± 0.42; p < 0.001; Figure 6A), DMN (12.07 ± 1.1 vs. 0.07 ± 0.07; p < 0.001; Figure 7A), and mNTS (17.77 ± 1.66 vs. 0.17 ± 0.11; p < 0.001; Figure 8A) compared to the control group
These findings support the hypothesis that phoenixin expression correlates with the magnitude of the stress response and suggest that an increase in phoenixin expression in the mNTS is a more general stress-related response triggered by several stressors, while other nuclei are likely activated by stress-specific triggers
Summary
Interest in phoenixin, with its 14 and 20 amino acid sequences, has continuously increased and its functions in basic physiological processes have become more and more apparent. Phoenixin was first described in 2013 as a peptide involved in reproduction [1], but has since been shown to be involved in multiple processes such as pain sensitivity [2], pruritus [3], inhibition of anxiety [4,5], increased food intake [6,7], influence of vasopressin secretion [8], as well as stress mediation [9]. Phoenixin’s effects of increasing food intake after intracerebroventricular (ICV) injection correlated with a distinct increase in activity in nesfatin-1 positive neurons in several brain nuclei, giving rise to speculatively counterbalancing roles of these two peptides [6]. A similar counterbalancing effect was observed regarding anxiety, where phoenixin is negatively correlated with levels of anxiety [4,5], while nesfatin-1 shows a positive correlation with anxiety in women [11,12]
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