%0 Journal Article
%T Chronic intermittent hypoxia affects endogenous serotonergic inputs and expression of synaptic proteins in rat hypoglossal nucleus
%A Cuiping Fu
%A Huan Lu
%A Juan Wang
%A Lijuan Hu
%A Shanqun Li
%A Wankun Gong
%A Xu Wu
%A Zilong Liu
%J Archive of "American Journal of Translational Research".
%D 2017
%X Evidence has shown that hypoxic episodes elicit hypoglossal neuroplasticity which depends on elevated serotonin (5-HT), in contrast to the rationale of obstructive sleep apnea (OSA) that deficient serotonergic input to HMs fails to keep airway patency. Therefore, understanding of the 5-HT dynamic changes at hypoglossal nucleus (HN) during chronic intermittent hypoxia (CIH) will be essential to central pathogenic mechanism and pharmacological therapy of OSA. Moreover, the effect of CIH on BDNF-TrkB signaling proteins was quanti£¿ed in an attempt to elucidate cellular cascades/synaptic mechanisms following 5-HT alteration. Male rats were randomly exposed to normal air (control), intermittent hypoxia of 3 weeks (IH3) and 5 weeks (IH5) groups. Through electrical stimulation of dorsal raphe nuclei (DRN), we conducted amperometric technique with carbon fiber electrode in vivo to measure the real time release of 5-HT at XII nucleus. 5-HT2A receptors immunostaining measured by intensity and c-Fos quanti£¿ed visually were both determined by immunohistochemistry. CIH significantly reduced endogenous serotonergic inputs from DRN to XII nucleus, shown as decreased peak value of 5-HT signals both in IH3 and IH5groups, whereas time to peak and half-life period of 5-HT were unaffected. Neither 5-HT2A receptors nor c-Fos expression in HN were signi£¿cantly altered by CIH. Except for marked increase in phosphorylation of ERK in IH5 rats, BDNF-TrkB signaling and synaptophys consistently demonstrated downregulated levels. These results suggest that the deficiency of 5-HT and BDNF-dependent synaptic proteins in our CIH protocol contribute to the decompensated mechanism of OSA
%K Obstructive sleep apnea
%K hypoglossal nucleus
%K serotonin
%K chronic intermittent hypoxia
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340689/