Proceedings of The Physiological Society

Future Physiology (Leeds, UK) (2017) Proc Physiol Soc 39, PC20

Poster Communications

Fluoxetine hydrochloride induced high levels of cell proliferation on brainstem and hippocampus of postnatal mice

N. Ghani1, I. Kearns1, A. Schoot1, J. Deuchars1, S. A. Deuchars1

1. University of Leeds, Leeds, West Yorkshire, United Kingdom.

Neurogenesis is the differentiation of neural stem cells into neurones, astrocytes and oligodendrocytes. Neurogenic niches have been identified in the hippocampus and subventricular zone which can be influenced by increased serotonergic signalling (Faillace, Zwiller and Bernabeu 2015) , but there is also evidence for postnatal neurogenesis in the brainstem, particularly in the dorsal vagal complex (DVC) (Bauer et al. 2005) . The DVC consists of the area postrema (AP), dorsal motor nucleus of vagus nerve (DMX) and nucleus of the solitary tract (NTS) (Leslie 1985). We therefore sought to determine whether modulation of serotonergic signalling can influence neurogenesis in the brainstem, comparing this with hippocampus. Six adolescent (6-8 weeks old) male and female C57/B16 mice (20-25 g), were housed in a 12-hour light/dark cycle with ad libitum access to food and water. This study investigated whether neurogenesis in the hippocampus and brainstem was modulated by the in vivo administration of the selective serotonin reuptake inhibitor fluoxetine (FLX), at 10 mg/kg/day for 10 days. 5-ethynyl-2'-deoxyuridine (EdU, 10mM), a thymidine analogue, was administered with FLX for a subsequent 5 days prior to sacrifice to allow the post hoc detection of newly proliferated cells. Using the dorsal region of the dentate gyrus as a positive control, FLX group had greater numbers proliferating cells within, (50.03 ± 2.15 EdU-positive cells per 50 μm section (n = 38)) compared to the control sections (30.71 ± 2.97 (n = 17); p < 0.05). Treatment with FLX caused a significantly (p<0.05) greater degree of EdU-labelling in the DVC (32.71 ± 3.45 (n = 35 sections) compared to the control group, (19.87 ± 1.64 (n = 38 sections). Each specific region of the DVC was individually investigated and it showed FLX-treated mice had significantly greater number of EdU-labelled cells per 50 µm compared to control group in DMX (4.54 ± 0.49 vs 3.16 ± 0.34, p<0.05), NTS (22.43 ± 2.65 vs 14.37 ± 1.26, p<0.05) and AP (10.05 ± 0.99 vs 4.94 ± 0.57, p<0.05). Within the DVC, a similar pattern of distribution of EdU-positive cells was observed in the control and FLX-treated mice, the majority was detected in NTS (64% in the control and 61% in the FLX-treated group). The AP contained 22% and 27% of the EdU-positive cells in the whole DVC, in the control and FLX-treated groups respectively. In conclusion, these results suggest that serotonin promotes high levels of cell proliferation in the DVC region of the brainstem and which may prove interesting in the light of the diverse functional roles of this region.

Where applicable, experiments conform with Society ethical requirements