RESUMO
Sevoflurane inhalation is prone to initiate cognitive deficits in infants. The early growth response-2 (Egr-2) gene is DNA-binding transcription factor, involving in cognitive function. In this study we explored the molecular mechanisms underlying the vulnerability to cognitive deficits after sevoflurane administration. Six-day-old (young) and 6-week-old (early adult) mice received anesthesia with 3% sevoflurane for 2 h daily for 3 days. We showed that multiple exposures of sevoflurane induced significant learning ability impairment in young but not early adult mice, assessed in Morris water maze test on postnatal days 65. The integrated differential expression analysis revealed distinct transcription responses of Egr family members in the hippocampus of the young and early adult mice after sevoflurane administration. Particularly, Egr2 was significantly upregulated after sevoflurane exposure only in young mice. Microinjection of Egr2 shRNA recombinant adeno-associated virus into the dentate gyrus alleviated sevoflurane-induced cognitive deficits, and abolished sevoflurane-induced dendritic spins loss and BDNF downregulation in young mice. On the contrary, microinjection of the Egr2 overexpression virus in the dentate gyrus aggravated learning ability impairment induced by sevoflurane in young mice but not early adult mice. Furthermore, we revealed that sevoflurane markedly upregulated the nuclear factors of activated T-cells NFATC1 and NFATC2 in young mice, which were involved in Egr2 regulation. In conclusion, Egr2 serves as a critical factor for age-dependent vulnerability to sevoflurane-induced cognitive deficits.
Assuntos
Anestésicos Inalatórios , Disfunção Cognitiva , Proteína 2 de Resposta de Crescimento Precoce , Éteres Metílicos , Animais , Camundongos , Anestésicos Inalatórios/toxicidade , Animais Recém-Nascidos , Cognição , Disfunção Cognitiva/induzido quimicamente , Proteína 2 de Resposta de Crescimento Precoce/genética , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto , Sevoflurano/efeitos adversosRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with recurrent intestinal inflammation. Although the exact etiology of IBD remains unknown, the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors. The role of the gut microbiota, particularly the bidirectional interaction between the brain and gut microbiota, has gradually attracted more attention. AIM: To investigate the potential effect of spinal anesthesia on dextran sodium sulfate (DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD. METHODS: A DSS-induced colitis mice model was established. Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation (FMT) to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved. RESULTS: We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms, including reduced body weight loss, decreased disease activity index score, improved intestinal permeability and colonic morphology, decreased inflammatory response, and enhanced intestinal barrier functions. Moreover, spinal anesthesia significantly increased the abundance of Bacteroidetes, which was suppressed in the gut microbiota of colitis mice. Interestingly, cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes. We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS, which might affect the gut microbiota. CONCLUSION: These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota, which highlights a novel approach for the treatment of IBD.
Assuntos
Raquianestesia , Anestésicos , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Raquianestesia/efeitos adversos , Anestésicos/efeitos adversos , Animais , Bacteroidetes , Colite/tratamento farmacológico , Colite/terapia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , SulfatosRESUMO
Light can possess orbital angular momentum (OAM), in addition to spin angular momentum (SAM), which offers nearly infinite possible values of momentum states, allowing a wider degree of freedom for information processing and communications. The OAM of light induces a selection rule that obeys the law of conservation of angular momentum as it interacts with a material, affecting the material's optical and electrical properties. In this work, silicon nanowire field-effect transistors are subjected to light with OAM, also known as twisted light. Electrical measurements on the devices consequently reveal photocurrent enhancements after incrementing the OAM of the incident light from 0â (fundamental mode) to 5â. Such a phenomenon is attributed to the enhancements of the photogating and the photoconductive effects under the influence of the OAM of light, the underlying mechanism of which is proposed and discussed using energy band diagrams. With these observations, a strategy for controlling photocurrent has been introduced, which can be a realization of the application in the field of optoelectronics technology.
RESUMO
Neuropathic pain (NP) is an intractable disease accompanying with allodynia, hyperalgesia and spontaneous pain. Accumulating evidence suggested that large volume of neurotransmitters, genes, and signaling pathways were implicated with the initiation and development of NP, while the underlying mechanism still remained poorly understood. Therefore, it was extremely important to further elucidate the potential regulatory networks for developing appropriate treatment options. Here, the RNA-Seq high-throughput sequencing was employed to determine the genes expression change in mice undergoing spinal nerve ligation (SNL). Meanwhile, the differentially expressed genes (DEGs) were analyzed by using integrated Differential Expression and Pathway analysis (iDEP) tools and String database. Then, quantitative real-time PCR (qRT-PCR) was employed to detect the expression of hub gens. The results showed that the DEGs mainly comprised 1712 upregulated and 1515 downregulated genes at 7 days, and consisted of 243 upregulated and 357 downregulated genes at 28 days after surgery, respectively. Additionally, 133 genes and two pathways including retrograde endocannabinoid signaling and cardiac muscle contraction collectively participated in biological reactions of 7th and 28th day after operation. Moreover, the results showed that the mRNA and protein expression of Ccl5, Cacna2d1, Cacna2d2, Cacnb2, Gabrb3, GluA1, and GluA2 were significantly upregulated in SNL-7/28d group than that of in Sham-7/28d group (SNL-7d vs. Sham-7d; SNL-28d vs. Sham-28d; P < 0.05). And the level of Glra2, Glra4, Glra3, Grik1, Grik2, NR1, NR2A, and NR2B was obviously increased in SNL-7d group compared to Sham-7d group (P < 0.05), but which was no statistical difference between SNL-28d group and Sham-28d group. Therefore, these results provided new perspectives and strategies for deeply illuminating the underlying mechanism, and identifying the key elements for treating NP.