Chronic intermittent hypoxia affects endogenous serotonergic inputs and expression of synaptic proteins in rat hypoglossal nucleus.
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 quantiﬁed 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-HT2Areceptors immunostaining measured by intensity and c-Fos quantiﬁed 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-HT2Areceptors nor c-Fos expression in HN were signiﬁcantly 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.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityShanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan UniversityShanghai 200032, China.
Xu
X
Wu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityShanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan UniversityShanghai 200032, China.
Huan
H
Lu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University Shanghai, China.
Lijuan
L
Hu
Department of Pharmacology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Research, Shanghai Medical College of Fudan University Shanghai 200032, China.
Wankun
W
Gong
Department of Pharmacology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Research, Shanghai Medical College of Fudan University Shanghai 200032, China.
Juan
J
Wang
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityShanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan UniversityShanghai 200032, China.
Cuiping
C
Fu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityShanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan UniversityShanghai 200032, China.
Zilong
Z
Liu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityShanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan UniversityShanghai 200032, China.
Shanqun
S
Li
Obstructive sleep apnea; chronic intermittent hypoxia; hypoglossal nucleus; serotonin