ABSTRACT
Objective: Obstructive sleep apnea (OSA) seriously affects the children's cognitive functions, but the neuroimaging mechanism of cognitive impairment is still unclear. The purpose of our study was to explore the difference in brain local gray matter volume (GMV) between children with OSA and non-OSA, and the correlation between the difference regions of brain gray matter volume and cognitive, the severity of OSA. Method: Eighty-three children aged 8-13 years were recruited in our study, 52 children were diagnosed as OSA by polysomnography, and 31 as the non-OSA. All the subjects were underwent high-resolution 3-dimensional T1-weighted magnetic resonance images. The voxel-based morphometry (VBM) was be used to analyse the local GMV. The Das-Naglieri cognitive assessment system (DN: CAS) was used to assess the subjects' cognitive. The difference of local GMV between the two groups was analyzed by two-sample T-test. The PSG variables and the scores of DN: CAS between the OSA group and non-OSA group were compared by independent samples t-tests. Pearson correlation was used to calculate the association between the difference areas of gray matter volumes in brain and DN: CAS scores, obstructive apnea/hypopnea index (OAHI, an index of the severity of OSA). Results: The gray matter volume of the right Middle Frontal Gyrus (MFG_R) in OSA children were larger than the non-OSA children, and the OSA children had lower scores of the Word Series in DN: CAS. There was negative correlation between the scores of Expressive Attention in DN: CAS and the gray matter volume of the right middle frontal gyrus, and it was no significantly correlation between OAHI and the gray matter volume of the right middle frontal gyrus. Conclusion: Our results suggest that the development of gray matter volume in frontal cortex, which associated with attention, were sensitive to the effects of OSA, provides neuroimaging evidence for cognitive impairment in children with OSA.
ABSTRACT
OBJECTIVE: Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is a sleep respiratory disease associated with cognitive impairment, The nuclear factor erythroid 2 related factor 2 (Nrf2) plays a neuroprotective role. This study was designed to investigate the mechanism of Nrf2 protecting neural cells from endoplasmic reticulum stress (ERS), induced by chronic intermittent hypoxia (CIH) and sleep fragmentation (SF) which caused cognitive impairment in mice. METHODS: Establishment of CIH and SF mice to simulate OSAHS mouse model. An eight-arm maze behavior test measured the cognitive function of mice, and Nissl staining and TUNEL staining were used to detect pathological changes in hippocampal neurons. The expression of ERS and Nrf2 and its downstream related mRNAs and proteins were detected by qRT-PCR and Western blotting. RESULTS: CIH and SF lead to cognitive impairment in mice, and Sulforaphane (SFN, Nrf2 agonist) plays a protective role, while Nrf2-KO aggravates the cognitive impairment. CIH and SF reduced the number of Nissl bodies in neurons and induced apoptosis. The mRNA levels of BiP, CHOP, Nrf2, GCLC and Prdx1 in CIH, SF and CIH + SF groups were increased (p = 0.001), whereas the mRNA levels of BiP and CHOP in the CIH + SF + SFN group were decreased (p = 0.02) while those of Nrf2 and Prdx1 were increased (p = 0.005). The CIH + SF + Nrf2-KO group, the mRNA levels of CHOP were increased (p = 0.001) while Nrf2, GCLC and Prdx1 were decreased (p = 0.001). The protein levels of CHOP and active Caspase-12 in CIH, SF, CIH + SF and CIH + SF + Nrf2-KO groups were increased (p = 0.03), while those of Prdx1 and Nrf2 were increased (p = 0.03) in the CIH + SF + SFN group, while decreased (p = 0.02) in the Nrf2-KO group. CONCLUSIONS: Chronic intermittent hypoxia(CIH) and sleep fragmentation(SF) could aggravate the inflammatory response of nerve cells through endoplasmic reticulum stress, leading to apoptosis of nerve cells, and causing cognitive impairment in mice.Nrf2 alleviates cognitive impairment induced by chronic intermittent hypoxia and sleep fragmentation by modulating endoplasmic reticulum stress. Activation of Nrf2 protects cognitive impairment through the Nrf2-Prdx1 signaling pathway.
