Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity.

BACKGROUND: Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. METHODS: Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. RESULTS: Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. CONCLUSIONS: Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

The effect of sevoflurane exposure on cell-type-specific changes in the prefrontal cortex in young mice.

Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10. Behavioral tests and single-nucleus RNA sequencing (snRNA-seq) of the PFC were conducted from PNDs 31 to 37. Mechanistic exploration included clustering analysis, identification of differentially expressed genes (DEGs), enrichment analyses, single-cell trajectory analysis, and genome-wide association studies (GWAS). Sevoflurane anesthesia resulted in sociability and cognition impairments in mice. Novel specific marker genes identified 8 distinct cell types in the PFC. Most DEGs between the control and sevoflurane groups were unique to specific cell types. Re-defining 15 glutamatergic neuron subclusters based on layer identity revealed their altered expression profiles. Notably, sevoflurane disrupted the trajectory from oligodendrocyte precursor cells (OPCs) to oligodendrocytes (OLs). Validation of disease-relevant candidate genes across the main cell types demonstrated their association with social dysfunction and working memory impairment. Behavioral results and snRNA-seq collectively elucidated the cellular atlas in the PFC of young male mice, providing a foundation for further mechanistic studies on developmental neurotoxicity induced by anesthesia.

Can internet use change sport participation behavior among residents? Evidence from the 2017 Chinese General Social Survey.

Purpose: The popularization of the internet has promoted the implementation of China's national fitness strategy and created conditions for Chinese residents to participate in sports. The internet is an essential medium for disseminating sports knowledge, and the use of the internet can change sport participation behaviors. Therefore, the internet can be used to popularize sports knowledge and promote the participation of all people in sports and thus improve the health of the entire population. This study attempts to empirically analyse how the use of the internet changes sport participation behavior. Method: Utilizing data from the 2017 China General Social Survey, a probit model, ivprobit model, and bias-corrected non-parametric percentile bootstrap test were used to analyse the impact of internet use on sport participation behavior. Results: The empirical results show that internet use significantly increased the probability of participation in sports by Chinese residents. Heterogeneity test results showed that internet use was more effective in promoting sport participation in middle-aged groups, groups of older persons, unmarried groups, and groups with a high school education or above. The mediating effect test results showed that internet use influenced residents' participation in sports by promoting social interaction, leisure and entertainment, and learning and recharging. Conclusions: The internet has changed participation in sports; specifically, the use of the internet promotes sport participation. Additionally, internet use has a more obvious impact on improving the sport participation behavior of middle-aged, older, unmarried, and middle- and higher-educated individuals. Internet social interaction, internet entertainment and internet learning are effective channels to encourage Chinese residents to participate in sports and improve their health.

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction.

BACKGROUND: Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. METHODS: Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. RESULTS: LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. CONCLUSIONS: Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

[Adaptive changes in activity of tonoplast H(+)-ATPase from the roots of tomato seedlings under phosphorus starvation].

We studied the growth state of tomato seedlings and the adaptive changes in activity of tonoplast H(+)-ATPase on different days (5 d, 7 d, 9 d, 11 d, 13 d) sampling from the roots of tomato seedlings under phosphorus starvation. The results indicated that the average height of the seedlings decreased under phosphorus starvation, while the main roots of the seedlings were significantly longer than those of the control. The phosphorus uptake rates of tomato seedlings under phosphorus starvation significantly increased and were much higher than those of controls and reached maximum values under the starvation for 7 days. The tonoplast H(+)-ATPase activity in the roots of tomato seedlings increased under phosphorus starvation and reached maximum values under the starvation for 7 days, while the activity of the control changed little. Kinetic analysis of tonoplast H(+)-ATPase showed that phosphorus starvation significantly lowered the K(m) value, but had no significant effect on the V(max) value of the enzyme. The results showed that phosphorus starvation increased the affinity of the enzyme to its substrate. In addition, phosphorus starvation did not alter the optimum pH (7.5) of the ATPase activity.