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Vectorial optical fields (VOFs) with extra degrees of freedom hold promise for many photonic applications. However, current methods to generate VOFs are either bulky in size or exhibit limited functionalities. Here, we demonstrate a tunable VOF generator by exciting plasmonic surface lattice resonances (SLRs) with axial symmetry. By meticulously arranging bilayer circular arrays with opposite handedness, we achieve a high Q-factor of 103 via just a few particles despite the general belief that too small array size suppresses the SLRs. This work presents tunable complex VOFs with distinct inhomogeneous spatial polarization distributions, which may enable various applications in integrated and polarization optics.
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Submerged plants play a significant role in the remediation and purification of polluted water bodies. Reconstruction of submerged plants has been considered as an important ecological method to restore aquatic ecosystems. However, large-scale and efficient plantation of submerged plants in water restoration is a huge challenge. This paper proposes a novel mechanized planting method for submerged plants utilizing nutrition pots as planting units. Firstly, the details of the mechanized planting method were introduced. The mechanized planting method involves pre-planting the reproductive bodies of submerged plants in degradable nutrition pots, and then implanting them into the underwater soil through a planting device. Secondly, the interaction force between the nutrition pot and the soil was measured. It was found that the implantation force of nutrition pots increases with planting velocity. The planting force shows a significant increase trend when the water content in the soil decreases. Thirdly, the deformation of the nutrition pot was studied through simulations. It was discovered that the deformation of the nutrition pot mainly occurs at the bottom and the side walls near the bottom, and the limited deformation ensures the integrity of the nutrition pot. Finally, a planting device with a linear motion mechanism was designed, and a typical submerged plant, Vallisneria natans was tested, using agricultural paper seedling containers as the nutrition pots. It was demonstrated that the mechanized device successfully planted submerged plant nutrition pots into the soil, and the submerged plants survived and showed a clear growth trend. The mechanized planting method of submerged plants proposed in this article is expected to provide a new and friendly technology for ecological restoration of water source.
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Ecosistema , Restauración y Remediación Ambiental/métodos , Suelo , Biodegradación AmbientalRESUMEN
Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.
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Depresión , Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Ratones Endogámicos C57BL , Microglía , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Derrota Social , Estrés Psicológico , Canal Aniónico 1 Dependiente del Voltaje , Animales , Mitocondrias/metabolismo , Depresión/metabolismo , Microglía/metabolismo , Microglía/patología , Ratones , Masculino , Retículo Endoplásmico/metabolismo , Estrés Psicológico/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/genética , Hipocampo/metabolismo , Hipocampo/patología , Adenosina Trifosfato/metabolismo , Inflamasomas/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Calcio/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Conducta Animal , Membranas Asociadas a Mitocondrias , Proteínas HSP70 de Choque TérmicoRESUMEN
Tall clonal grasses commonly display competitive advantages with nitrogen (N) enrichment. However, it is currently unknown whether the height is derived from the vegetative or reproductive module. Moreover, it is unclear whether the height of the vegetative or reproductive system regulates the probability of extinction and colonization, and determines species diversity. In this study, the impacts on clonal grasses were studied in a field experiment employing two frequencies (twice a year vs. monthly) crossing with nine N addition rates in a temperate grassland, China. We found that the N addition decreased species frequency and increased extinction probability, but did not change the species colonization probability. A low frequency of N addition decreased species frequency and colonization probability, but increased extinction probability. Moreover, we found that species reproductive height was the best index to predict the extinction probability of clonal grasses in N-enriched conditions. The low frequency of N addition may overestimate the negative effect from N deposition on clonal grass diversity, suggesting that a higher frequency of N addition is more suitable in assessing the ecological effects of N deposition. Overall, this study illustrates that reproductive height was associated with the clonal species extinction probability under N-enriched environment.
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BACKGROUND: Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. METHODS: A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. RESULTS: Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are â≥1â mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCRâ>â30â mL/min. Our simulations suggest 10â mg/kg for patients with CLCR between 30 and 90â mL/min, and 12â mg/kg for patients with CLCR higher than 90â mL/min. CONCLUSIONS: This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.
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Antibacterianos , Enfermedad Crítica , Daptomicina , Oxigenación por Membrana Extracorpórea , Método de Montecarlo , Humanos , Daptomicina/farmacocinética , Daptomicina/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Anciano , Pruebas de Sensibilidad Microbiana , Espectrometría de Masas en Tándem , Infecciones por Bacterias Grampositivas/tratamiento farmacológicoRESUMEN
Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.
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Dolor Crónico , Neuralgia del Trigémino , Animales , Ratones , Adenosina/farmacología , Adenosina Trifosfato/farmacología , Modelos Animales de Enfermedad , Hipocampo , MicroglíaRESUMEN
Persistent hyperplastic primary vitreous (PHPV) is a rare congenital developmental ocular disorder caused by incomplete regression of the embryonic hyaloid vasculature; bilateral presentations are even rarer. We report a 6-year-old child with bilateral PHPV who visited our hospital for strabismus, without exhibiting leukocoria, microphthalmia, and systemic diseases. These unique characteristics distinguish our case from other cases of PHPV. It is crucial to increase awareness of congenital eye disease in children and the importance of performing fundus examination with the pupils dilated.
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Vítreo Primario Hiperplásico Persistente , Estrabismo , Niño , Humanos , Hiperplasia , Estrabismo/diagnóstico , Estrabismo/etiología , Ojo , CaraRESUMEN
Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.
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Hormona Liberadora de Corticotropina , Neuralgia del Trigémino , Humanos , Hormona Liberadora de Corticotropina/metabolismo , Neuralgia del Trigémino/etiología , Neuralgia del Trigémino/metabolismo , Neuronas/metabolismo , Hipocampo/fisiología , Dolor/metabolismoRESUMEN
BACKGROUND: To report a case of endophthalmitis in a silicone oil (SO)-filled eye associated with Staphylococcus cohnii. After vitrectomy, the environment for bacterial growth in the eye is removed, and SO has antibacterial effect on a variety of microorganisms. Endophthalmitis is seen in about 0.040% cases after pars plana vitrectomy and is even more uncommon in cases where SO is used. METHODS: The patient was diagnosed as endophthalmitis and admitted to our hospital for emergency. The main concern is if intraocular infection can be controlled and the visual prognosis. In this case, multiple intravitreal antibiotics injection and anterior chamber washout were performed. Not only that, phacoemulsification was performed. RESULTS: Hypopyon became less after 3 operations were performed. The infection was under control finally. CONCLUSION: To the best of our knowledge, it is the first report of S. cohnii endophthalmitis in an SO-filled globe of an middle-aged patient. It is important to treat infective endophthalmitis with antibiotics promptly. Delayed therapy may affect the visual prognosis.
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Endoftalmitis , Infecciones Bacterianas del Ojo , Persona de Mediana Edad , Humanos , Vitrectomía/efectos adversos , Aceites de Silicona , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/etiología , Antibacterianos/uso terapéutico , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/etiología , Estudios RetrospectivosRESUMEN
Hormone supplementation is one of the common therapies for menopause-related disorders. Among different tools, the ovariectomy (OVX) rodents are widely accepted as an appropriate menopausal pain model. Our previous study has showed that OVX produces a significant pain facilitation in both acute pain and tonic pain, however, the underlying mechanisms remain unclear. In this study, we examined the effects of OVX treatment and estradiol (E2) supplementation on formalin-induced nociceptive responses, and explored the associated spinal mechanisms. Female Sprague-Dawley rats underwent bilateral OVX, and E2 supplementation was given subcutaneously from the 5th week after surgery (30 µg/day for 7 days). Our results showed that formalin-induced nociceptive behaviors did not differ between diestrus and proestrus stages of the estrous in intact rats. However, OVX exacerbated formalin-evoked inflammatory pain, especially in the late phase at 4-5 weeks but not 2 weeks post-surgery. E2 supplementation significantly reversed the OVX-triggered hyperalgesia. Double immunofluorescence staining revealed that both ERα and ERß in the spinal dorsal horn were co-labeled with the neuronal markers, but not with markers of astrocytes or microglia. The spinal ERα (but not ERß) expression significantly increased in the OVX group, which was reversed by E2 supplementation. Moreover, the OVX individuals showed an increased protein kinase B (AKT) level in lumbar spinal cord, and E2 supplementation diminished the AKT expression in OVX rats. Finally, intrathecal injection Wortmannin, an inhibitor for AKT signaling, effectively reduced the nociceptive behaviors in the late phase and the number of c-fos positive cells. Together, our findings indicate that E2 supplementation alleviates the OVX-induced hyperalgesia, which might be involved in spinal ERα and AKT mechanisms.
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Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin-Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7-/- mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection.
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Aminoglicósidos , Ototoxicidad , Animales , Ratones , Aminoglicósidos/toxicidad , Aminoglicósidos/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Ototoxicidad/metabolismo , Antibacterianos/toxicidad , Neomicina/toxicidad , Neomicina/metabolismo , Células Ciliadas Auditivas/metabolismo , Cóclea , Adenosina Trifosfato/metabolismoRESUMEN
The demethylase JmjC structural domain-containing protein 8 (JMJD8) has been demonstrated to be involved in cellular inflammatory responses. Neuropathic pain (NP) is a chronic pain, and it is unclear whether JMJD8 is involved in the regulation of NP. Using a chronic constriction injury (CCI) mouse model of NP, we investigated the expression levels of JMJD8 during NP and the influences of JMJD8 on regulating pain sensitivity. We found that JMJD8 expression in the spinal dorsal horn was reduced after CCI. Immunohistochemistry showed that JMJD8 was colabeled with GFAP in naïve mice. Knockdown of JMJD8 in the spinal dorsal horn astrocytes induced pain behavior. Further study showed that overexpression of JMJD8 in the spinal dorsal horn astrocytes not only reversed pain behavior but also activated the spinal dorsal horn A1 astrocytes. These results suggest that JMJD8 may modulate pain sensitivity by affecting activated the spinal dorsal horn A1 astrocytes and may be a potential therapeutic target for NP.
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Astrocitos , Neuralgia , Animales , Ratones , Astrocitos/metabolismo , Hiperalgesia/metabolismo , Neuralgia/metabolismo , Umbral del Dolor/fisiología , Médula Espinal/metabolismo , Asta Dorsal de la Médula Espinal/metabolismoRESUMEN
Pain and obesity, as well as their associated impairments, are major health concerns. Understanding the relationship between the two is the focus of a growing body of research. However, early researches attribute increased mechanical stress from excessive weight as the main factor of obesity-related pain, which not only over-simplify the association, but also fail to explain some controversial outcomes arising from clinical investigations. This review focuses on neuroendocrine and neuroimmune modulators importantly involved in both pain and obesity, analyzing nociceptive and anti-nociceptive mechanisms based on neuroendocrine pathways including galanin, ghrelin, leptin and their interactions with other neuropeptides and hormone systems which have been reported to play roles in pain and obesity. Mechanisms of immune activities and metabolic alterations are also discussed, due to their intense interactions with neuroendocrine system and crucial roles in the development and maintenance of inflammatory and neuropathic pain. These findings have implications for health given rising rates of obesity and pain-related diagnoses, by providing novel weight-control and analgesic therapies targeted on specific pathways.
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Neuralgia , Neuroinmunomodulación , Humanos , Obesidad/complicaciones , Obesidad/epidemiología , Sistemas Neurosecretores , ComorbilidadRESUMEN
Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.
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Derrota Social , Sinaptosomas , Animales , Ratones , Hipocampo , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Estrés PsicológicoRESUMEN
Light modulates mood through various retina-brain pathways. We showed that mice treated with short-term acute bright light exposure displayed anxiety-related phenotypes in a prolonged manner even after the termination of the exposure. Such a postexposure anxiogenic effect depended upon melanopsin-based intrinsically photosensitive retinal ganglion cell (ipRGC) activities rather than rod/cone photoreceptor inputs. Chemogenetic manipulation of specific central nuclei demonstrated that the ipRGC-central amygdala (CeA) visual circuit played a key role in this effect. The corticosterone system was likely to be involved in this effect, as evidenced by enhanced expression of the glucocorticoid receptor (GR) protein in the CeA and the bed nucleus of the stria terminalis and by the absence of this effect in animals treated with the GR antagonist. Together, our findings reveal a non-image forming visual circuit specifically designed for "the delayed" extinction of anxiety against potential threats, thus conferring a survival advantage.
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Núcleo Amigdalino Central , Células Ganglionares de la Retina , Ratones , Animales , Células Ganglionares de la Retina/metabolismo , Retina , Células Fotorreceptoras Retinianas Conos , Células Fotorreceptoras de Vertebrados/metabolismo , LuzRESUMEN
The medial prefrontal cortex (mPFC) is critical for both the sensory and emotional/cognitive components of pain. However, the underlying mechanism remains largely unknown. Here, we examined changes in the transcriptomic profiles in the mPFC of mice with chronic pain using RNA sequencing (RNA-seq) technology. A mouse model of peripheral neuropathic pain was established via chronic constriction injury (CCI) of the sciatic nerve. CCI mice developed sustained mechanical allodynia and thermal hyperalgesia, as well as cognitive impairment four weeks after surgery. RNA-seq was conducted 4 weeks after CCI surgery. Compared with contral group, RNA-seq identified a total 309 and 222 differentially expressed genes (DEGs) in the ipsilateral and contralateral mPFC of CCI model mice, respectively. GO analysis indicated that the functions of these genes were mainly enriched in immune- and inflammation-related processes such as interferon-gamma production and cytokine secretion. KEGG analysis further showed the enrichment of genes involved in the neuroactive ligand-receptor interaction signaling pathway and Parkinson disease pathway that have been reported to be importantly involved in chronic neuralgia and cognitive dysfunction. Our study may provide insights into the possible mechanisms underlying neuropathic pain and pain-related comorbidities.
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Hiperalgesia , Neuralgia , Ratones , Animales , Constricción , Hiperalgesia/genética , Neuralgia/genética , Perfilación de la Expresión Génica , Corteza Prefrontal/metabolismoRESUMEN
Neuropathic pain seriously affects people's life, but its mechanism is not clear. Interleukin-17 (IL-17) is a proinflammation cytokine and involved in pain regulation. Our previous study found that IL-17 markedly enhanced the excitatory activity of spinal dorsal neurons in mice spinal slices. The present study attempts to explore if IL-17 contributes to neuropathic pain and spinal synapse plasticity. A model of spared nerve injury (SNI) was established in C57BL/6 J mice and IL-17a mutant mice. The pain-like behaviors was tested by von Frey test and dynamic mechanical stimuli, and the expression of IL-17 and its receptor, IL-17RA, was detected by immunohistochemical staining. C-fiber evoked field potentials were recorded in vivo. In the spinal dorsal horn, IL-17 predominantly expressed in the superficial spinal astrocytes and IL-17RA expressed mostly in neurons and slightly in astrocytes. The SNI-induced static and dynamic allodynia was significantly prevented by pretreatment of neutralizing IL-17 antibody (intrathecal injection, 2 µg/10 µL) and attenuated in IL-17a mutant mice. Post-treatment of IL-17 neutralizing antibody also partially relieved the established mechanical allodynia. Moreover, spinal long-term potentiation (LTP) of C-fiber evoked field potentials, a substrate for central sensitization, was suppressed by IL-17 neutralizing antibody. Intrathecal injection of IL-17 recombinant protein (0.2 µg/10 µL) mimicked the mechanical allodynia and facilitated the spinal LTP. These data implied that IL-17 in the spinal cord played a crucial role in neuropathic pain and central sensitization.
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Interleucina-17 , Neuralgia , Ratas , Ratones , Animales , Hiperalgesia/metabolismo , Ratas Sprague-Dawley , Ratones Endogámicos C57BL , Neuralgia/metabolismo , Médula Espinal/metabolismo , Sinapsis/metabolismoRESUMEN
Inflammatory microglia and P2X7R are involved in the development of stress-induced depression. Endoplasmic reticulum (ER) stress and mitochondrial damage play an important role in depression and microglial activation. Bullatine A (BLA) has anti-inflammatory and anti-rheumatic effects, and can be used as a P2X7R antagonist. We found that Bullatine A can effectively inhibit the calcium overload of mitochondria and the increase of ER and mitochondrial colocalization caused by eATP (extracellular ATP) in BV2-cells. Bullatine A can also inhibit the activation of PERK-elF-2α unfolded protein response (UPR), lysosome production and the increase of NLRP3 inflammasome protein expression in BV2-cells Both intragastric administration and intra-hippocampal microinjection of Bullatine A can significantly improve the despair behavior but not anhedonia of Chronic chronic social defeat stress (CSDS) mice. Bullatine A may have a beneficial therapeutic effect in treating diseases related to stress stimulation, such as depression.
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Inflamasomas , Microglía , Ratones , Animales , Inflamasomas/metabolismo , Microglía/metabolismo , Derrota Social , Antidepresivos/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés del Retículo EndoplásmicoRESUMEN
BACKGROUND AND PURPOSE: Patients suffering from trigeminal neuralgia are often accompanied by anxiety and depression. Microglia-mediated neuroinflammation is involved in the development of neuropathic pain and anxiodepression pathogenesis. Whether and how microglia are involved in trigeminal neuralgia-induced anxiodepression remains unclear. EXPERIMENTAL APPROACH: Unilateral constriction of the infraorbital nerve (CION) was performed to establish trigeminal neuralgia in rat and mouse models. Mechanical allodynia and anxiodepressive-like behaviours were measured. Optogenetic and pharmacological manipulations were employed to investigate the role of hippocampal microglia in anxiety and depression caused by trigeminal neuralgia. KEY RESULTS: Trigeminal neuralgia activated ipsilateral but not contralateral hippocampal microglia, up-regulated ipsilateral hippocampal ATP and interleukin-1ß (IL-1ß) levels, impaired ipsilateral hippocampal long-term potentiation (LTP) and induced anxiodepressive-like behaviours in a time-dependent manner in rodents. Pharmacological or optogenetic inhibition of ipsilateral hippocampal microglia completely blocked trigeminal neuralgia-induced anxiodepressive-like behaviours. Activation of unilateral hippocampal microglia directly elicited an anxiodepressive state and impaired hippocampal LTP. Knockdown of ipsilateral hippocampal P2X7 receptors prevented trigeminal neuralgia-induced microglial activation and anxiodepressive-like behaviours. Furthermore, we demonstrated that microglia-derived IL-1ß mediated microglial activation-induced anxiodepressive-like behaviours and LTP impairment. CONCLUSION AND IMPLICATIONS: These findings suggest that priming of microglia with ATP/P2X7 receptors in the ipsilateral hippocampus drives pain-related anxiodepressive-like behaviours via IL-1ß. An asymmetric role of the bilateral hippocampus in trigeminal neuralgia-induced anxiety and depression was uncovered. The approaches targeting microglia and P2X7 signalling might offer novel therapies for trigeminal neuralgia-related anxiety and depressive disorder.
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Neuralgia , Neuralgia del Trigémino , Ratones , Ratas , Animales , Neuralgia del Trigémino/patología , Microglía/patología , Roedores , Hipocampo , Hiperalgesia , Adenosina TrifosfatoRESUMEN
To obtain multifunctional materials suitable for guiding alveolar bone regeneration under infectious conditions, we prepared asymmetric membranes comprising space acquiring layer that involves fibroblast inhibitor poly(p-dioxanone-co-L-phenylalanine) (PDPA), an isolating dense layer that forms barrier between two layers and an osteogenesis inducing electrospinning layer which involves hydroxyapatite or hydroxyapatite & minocycline. Then the composition, crystallization, morphology, and hydrophilicity of asymmetric membranes were analyzed. Minocycline incorporated membranes controlled the expansion of Porphyromonas gingivalis (P. gingivalis) in vitro. Hydroxyapatite-incorporated asymmetric membranes promoted the expression of osteogenesis related genes RUNX2, OPN, ALP of MC3T3-E1 cells in vitro. The mineralization of MC3T3-E1 cells cultured with hydroxyapatite-incorporated asymmetric membranes were also promoted in vitro. Asymmetric membranes especially hydroxyapatite-incorporated ones guided the regeneration of the mandibular bone defect in vivo. Bone regeneration guided under infectious conditions was evaluated in a P. gingivalis infected alveolar bone defect model. Specifically, space acquiring layer containing asymmetric membranes effectively controlled connective tissue hyperplasia at defect sites. The excellent guided bone regeneration achieved by applying a single space acquiring layer membrane further indicates the importance of acquiring space actively to induce bone regeneration. Hydroxyapatite-minocycline incorporated symmetric membranes could simultaneously suppress alveolar bone reabsorption caused by infection and guide regeneration of defects. Therefore, the hydroxyapatite-minocycline incorporated asymmetric membrane may be more suitable to be applied in guiding regeneration of bone defects under complex infectious conditions.