Chloride Transport Research Articles

Inhibition of neutrophil elastase by the bacterial serine protease inhibitor ecotin in cystic fibrosis airway samples

Abstract Cystic fibrosis (CF), a prevalent fatal genetic condition in North America, disrupts respiratory function by impeding chloride ion transport across mucosal surfaces. This leads to the thickening of mucus, resulting in constant lung inflammation and elevated levels of neutrophils. Neutrophil elastase (NE), a potent serine protease crucial for host defense, is released by these neutrophils. However, in excess, NE can cause detrimental host tissue damage. Abundant in CF airways, NE is a key predictor of lung disease progression. While past studies have explored targeting NE in CF, no optimal inhibitors have reached clinics. Our study tested ecotin, a bacterial periplasmic serine protease inhibitor, for its potential to impede NE activity in CF airway samples and curb NE release from human neutrophils. Results show that ecotin significantly reduces NE activity in sputum samples obtained from several CF patients. Additionally, we found that ecotin inhibits NE release from neutrophils exposed to CF lung stimuli like Staphylococcus aureus bacteria. These results establish ecotin as a promising NE inhibitor in CF with clinical potential.

Research on the mechanism of chlorine corrosion resistance of graphite tailings modified recycled coarse aggregate concrete: Corrosion product transformation and multi-scale mathematical characterization model

This research investigated the impact of substituting sand with graphite tailings (GT) on the chloride ion erosion resistance of recycled aggregate concrete (RAC). The role of GT is to significantly inhibit the penetration of chloride ions into the interior and slow down the corrosion process. However, the durability of graphite tailings recycled aggregate concrete (GTRAC) still depends on the replacement rate of recycled aggregate. At the same time, a multi-scale dynamic model of physical adsorption-chemical binding-free transport and erosion of chloride ions in GTRAC were established based on unsteady viscous fluid force and molecular dynamics.

Durability life evaluation of marine infrastructures built by using carbonated recycled coarse aggregate concrete due to the chloride corrosive environment

Due to the harsh marine environment of chloride ion invasion and corrosion, the issues of long-term chloride transport and durability life evaluation for marine infrastructures constructed/maintained by recycled aggregate concrete (RAC) after enhancement remain poorly understood. For our studies, an accelerated carbonation modification method for recycled coarse aggregate (RCA) was adopted to prepare carbonated recycled coarse aggregate (CRCA) samples, and the macroproperties, i.e., apparent density and water absorption, of CRCA were enhanced by approximately 1.40-3.97% and 16.3-21.8%, respectively, compared with those of RCA. An in-door experiment for chloride transport into concrete specimens subjected to a simulated marine environment of alternating drying-wetting cycles was conducted. The chloride profiles and transport characteristics of carbonated recycled coarse aggregate concrete (CRCAC), recycled coarse aggregate concrete (RCAC), and natural coarse aggregate concrete (NCAC) were analysed and compared. The results indicated that the chloride penetration depths and concentrations of CRCAC were approximately 52.6-96.2% of those of RCAC, which highlighted the better chloride resistance of CRCAC. A chloride transport model for marine concrete structures with various coarse aggregate types in a corrosive marine environment was established. Taking a certain harbour wharf as an example, the durability life of this case considering the application of the CRCAC was evaluated based on the chloride transport model, and the durability life of the CRCAC structure was improved by approximately 28.10% compared with that of the RCAC. The CRCAC developed in this paper has improved mechanical performance and durability than those of RCAC, and it has the potential to replace the NCAC and further support the construction and maintenance of marine infrastructures.

Chloride binding by layered double hydroxides (LDH/AFm phases) and alkali-activated slag pastes: an experimental study by RILEM TC 283-CAM

Chloride binding by the hydrate phases of cementitious materials influences the rate of chloride ingress into these materials and, thus, the time at which chloride reaches the steel reinforcement in concrete structures. Chloride binding isotherms of individual hydrate phases would be required to model chloride ingress but are only scarcely available and partly conflicting. The present study by RILEM TC 283-CAM ‘Chloride transport in alkali-activated materials’ significantly extends the available database and resolves some of the apparent contradictions by determining the chloride binding isotherms of layered double hydroxides (LDH), including AFm phases (monosulfate, strätlingite, hydrotalcite, and meixnerite), and of alkali-activated slags (AAS) produced with four different activators (Na2SiO3, Na2O·1.87SiO2, Na2CO3, and Na2SO4), in NaOH/NaCl solutions at various liquid/solid ratios. Selected solids after chloride binding were analysed by X-ray diffraction, and thermodynamic modelling was applied to simulate the phase changes occurring during chloride binding by the AFm phases. The results of the present study show that the chloride binding isotherms of LDH/AFm phases depend strongly on the liquid/solid ratio during the experiments. This is attributed to kinetic restrictions, which are, however, currently poorly understood. Chloride binding by AAS pastes is only moderately influenced by the employed activator. A steep increase of the chloride binding by AAS occurs at free chloride concentrations above approx. 1.0 M, which is possibly related to chloride binding by the C–(N–)A–S–H gel in the AAS.

Balancing mechanical property and swelling behavior of bacterial cellulose film by in-situ adding chitosan oligosaccharide and covalent crosslinking with γ-PGA

Bacterial cellulose (BC) is an ideal candidate material for drug delivery, but the disbalance between the swelling behavior and mechanical properties limits its application. In this work, covalent crosslinking of γ-polyglutamic acid (γ-PGA) with the chitosan oligosaccharide (COS) embedded in BC was designed to remove the limitation. As a result, the dosage, time, and batch of COS addition significantly affected the mechanical properties and the yield of bacterial cellulose complex film (BCCF). The addition of 2.25 % COS at the incubation time of 0.5, 1.5, and 2 d increased the Young's modulus and the yield by 5.65 and 1.42 times, respectively, but decreased the swelling behavior to 1774 %, 46 % of that of native BC. Covalent γ-PGA transformed the dendritic structure of BCCF into a spider network, decreasing the porosity and increasing the swelling behavior by 3.46 times. The strategy balanced the swelling behavior and mechanical properties through tunning hydrogen bond, electrostatic interaction, and amido bond. The modified BCCF exhibited a desired behavior of benzalkonium chlorides transport, competent for drug delivery. Thereby, the strategy will be a competent candidate to modify BC for such potential applications as wound dressing, artificial skin, scar-inhibiting patch, and so on.

Investigation on chloride releasing from coral aggregates to cement paste in coral aggregate concrete

Coral aggregate concrete (CAC) is one of the most commonly used building materials in construction on marine islands, but the chlorides contained in the coral aggregates (CA) could affect the durability of CAC with steel bars embedded. In this paper, an analytical solution for the diffusion of chlorides from CA into the cement paste in CAC was derivated and the model was established. Studies on chloride releasing behaviours in CAC through an experimental setup of CAC interface specimens with five mixes were conducted. From the analytical model, the chloride diffusion coefficient DCl can be obtained and, different from other reported chloride diffusion coefficient from harden specimen, this coefficient could be the only factor that describes the chloride transport in CAC from the mixing stage. The chloride releasing rate αCl from CA was also calculated and quantified. The results show that the chloride release rate from CA decayed with time and significant chloride release occurred in the first 30 days from the mixture of raw materials, the released amount of chlorides from CA was positively correlated to the average pore size of cement pastes, and the chloride diffusion coefficient of CA in this study was 2–3 magnitudes higher than that of hardened cement paste.

Convection-diffusion-electromigration coupled numerical simulation of water and chloride in cement-based materials

The transport of chloride in cement-based materials is influenced by various factors, and the chloride diffusion coefficient in numerical models should be the steady-state value under specific conditions, which is difficult to obtain through traditional experiments. In this article, based on an improved non-contact resistivity instrument, the steady-state chloride diffusion coefficient and porosity of cement-based materials are characterized. Considering the acceleration effect of moisture convection and electric field on chloride transport, a numerical model for moisture and chloride transport coupling diffusion, convection, and electromigration is established. Based on the measured steady-state chloride diffusion coefficient and porosity values, the influence of interface transition zone (ITZ), electric field type, chloride binding effect, initial conditions, and boundary conditions on moisture and chloride transport is numerically analyzed. It is found that the increase of ITZ thickness, electric field strength, boundary concentration, and initial concentration can accelerate chloride transport. The chloride concentration distribution curve exhibits a “shoulder peak” caused by chloride binding effect, and its peak height and width are positively correlated with the chloride binding coefficient. In conclusion, this study aims to better understand the ion transport behavior inside cement-based materials under coupling of convection, diffusion, and electromigration, and identify the key factors influencing this behavior, which provide a feasible scheme for durable design of concrete construction in environments rich in erosive media.

A Halogen‐Bond‐Driven Artificial Chloride‐Selective Channel Constructed from 5‐Iodoisophthalamide‐based Molecules

AbstractDespite considerable emphasis on advancing artificial ion channels, progress is constrained by the limited availability of small molecules with the necessary attributes of self‐assembly and ion selectivity. In this study, a library of small molecules based on 5‐haloisophthalamide and a non‐halogenated isophthalamide were examined for their ion transport properties across the lipid bilayer membranes, and the finding demonstrates that the di‐hexyl‐substituted 5‐iodoisophthalamide derivative exhibits the highest level of activity. Furthermore, it was established that the highest active compound facilitates the selective chloride transport that occurs via an antiport‐mediated mechanism. The crystal structure of the compound unveils a distinctive self‐assembly of molecules, forming a zig‐zag channel pore that is well‐suited for the permeation of anions. Planar bilayer conductance measurements proved the formation of chloride selective channels. A molecular dynamics simulation study, relying on the self‐assembled component derived from the crystal structure, affirmed the paramount significance of intermolecular hydrogen bonding in the formation of supramolecular barrel‐rosette structures that span the bilayer. Furthermore, it was demonstrated that the transport of chloride across the lipid bilayer membrane is facilitated by the synergistic effects of halogen bonding and hydrogen bonding within the channel.

A Halogen-Bond-Driven Artificial Chloride-Selective Channel Constructed from 5-Iodoisophthalamide-based Molecules.

Despite considerable emphasis on advancing artificial ion channels, progress is constrained by the limited availability of small molecules with the necessary attributes of self-assembly and ion selectivity. In this study, a library of small molecules based on 5-haloisophthalamide and a non-halogenated isophthalamide were examined for their ion transport properties across the lipid bilayer membranes, and the finding demonstrates that the di-hexyl-substituted 5-iodoisophthalamide derivative exhibits the highest level of activity. Furthermore, it was established that the highest active compound facilitates the selective chloride transport that occurs via an antiport-mediated mechanism. The crystal structure of the compound unveils a distinctive self-assembly of molecules, forming a zig-zag channel pore that is well-suited for the permeation of anions. Planar bilayer conductance measurements proved the formation of chloride selective channels. A molecular dynamics simulation study, relying on the self-assembled component derived from the crystal structure, affirmed the paramount significance of intermolecular hydrogen bonding in the formation of supramolecular barrel-rosette structures that span the bilayer. Furthermore, it was demonstrated that the transport of chloride across the lipid bilayer membrane is facilitated by the synergistic effects of halogen bonding and hydrogen bonding within the channel.

Identification of an ultra-rare Alu insertion in the CFTR gene: Pitfalls and challenges in genetic test interpretation

Cystic fibrosis (CF) is a life-limiting genetic disorder characterized by defective chloride ion transport due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Early detection through newborn screening programs significantly improves outcomes for individuals with CF by enabling timely intervention. Here, we report the identification of an Alu element insertion within the exon 15 of CFTR gene, initially overlooked in standard next-generation sequencing analyses. However, using traditional molecular techniques, based on polymerase chain reaction and Sanger sequencing, allowed the identification of the Alu element and the reporting of a correct diagnosis. Our analysis, based on bioinformatics tools and molecular techniques, revealed that the Alu element insertion severely affects the gene expression, splicing patterns, and structure of CFTR protein. In conclusion, this study emphasizes the importance of how the integration of human expertise and modern technologies represents a pivotal step forward in genomic medicine, ensuring the delivery of precision healthcare to individuals affected by genetic diseases.

Chloride transport in high-cycle fatigue-damaged concrete

This paper explored the penetration of chloride into concrete damaged by high-cycle compressive fatigue loading. Two environmental conditions including immersion and wetting-drying cycles were prepared for experimentally investigating the transport performance of chloride in fatigue-damaged concrete. Additionally, a prediction model was developed with the damage index of residual strain. Test results revealed that both apparent diffusion coefficients and contents of chloride at each depth increased in fatigue-damaged concrete, indicating that the fatigue damage significantly degraded the resistance of concrete to chloride penetration. Furthermore, for fatigue damaged concretes with extremely different fatigue cycles and load levels but the same residual strain, the chloride ion content profiles were highly overlapped, which demonstrated the reasonability of selecting residual strains as fatigue damage indexes. The applicability of the transport model was firstly validated with the measured chloride contents and then the chloride transport behavior in gradient fatigue-damaged concrete was investigated numerically using the validated model. The numerical results indicated that the chloride transport was more sensitive to the residual strain at the exposed edge than to the residual curvature and the effect of the later can be neglected.

Non-destructive characterization of pore structure and chloride diffusion coefficient of cementitious materials with modified non-contact electrical resistivity method

The intricate pore structure of cement-based materials passively influences chloride ion transport and mechanical properties. Existing non-contact electrical resistivity measurement (NC-ERM) methods lack precision for rigorous studies. the NC-ERM was upgraded in this research, which is suitable for assessing the pore structure and transport characteristics of hardened cementitious substrates. The results obtained from this method closely correspond to those obtained from CEMHYD3D, Mercury intrusion porosimetry (MIP), and other methods. Additionally, the impact of mixture proportions on the resistivity, pore structure parameters, and chloride ion diffusion coefficient of cementitious materials is discussed. With an increase in sand ratio and sand-to-stone ratio, the resistivity exhibits an initial rise followed by a decline. Chloride diffusion of 5 wt% NaCl-saturated specimens is 1.2–1.3 times higher than 3.5 wt% NaCl. This study provides a novel non-destructive, convenient and accurate method for characterising the pore structure and testing the transport properties of cementitious materials.

A Review of Chloride Corrosion Resistance of Ultra-High-Performance Concret

Extending the service life of reinforced concrete structures can effectively reduce the economic, environmental, resource and energy costs throughout their life cycle. However, a large number of reinforced concrete structures often suffer from corrosion of reinforcing bars due to chloride ion erosion in various environments, which leads to deterioration of performance, the loss of functionality and even safety accidents. As a barrier between reinforcing steel and the external environment, protective layer concrete can effectively prevent chloride ions from contacting the surface of reinforcing steel, thus delaying the corrosion of reinforcing steel and improving the durability of reinforced concrete structures. Ultra-high-performance concrete has a dense microstructure due to its low water-to-cement ratio and elimination of coarse aggregates, which can greatly impede the transport of chloride ions within it, and thus it is expected to significantly improve the service life of reinforced concrete infrastructure. Based on this, this paper firstly summarizes the basic mechanism of chloride ion transport inside cementitious materials, including the movement mode and physicochemical binding mechanism of chloride ions inside the cementitious, and analyzes the current research status and improvement methods of the chloride ion penetration and chloride ion binding capacity of ultra-high-performance concrete.

Outcomes of ERCP in Patients With Cystic Fibrosis: A Nationwide Inpatient Assessment.

Cystic fibrosis (CF) is a multisystem disorder that leads to abnormal transport of chloride and sodium across secretory epithelia resulting in thickened, viscous secretions in the bronchi, biliary tract, pancreas, intestine, and the reproductive system. Defects in the biliary tract can predispose to stone formation requiring endoscopic retrograde cholangiopancreatography (ERCP). However, there is a paucity of data assessing ERCP outcomes in patients with CF. We identified patients from the Healthcare Cost and Utilization Project (HCUP)-National Inpatient Sample (NIS) between the years 2016 and 2020. Our study group included patients with CF of all ages who underwent an inpatient ERCP. We used ICD10 diagnostic and procedural codes to identify patients, procedures, and complications of the procedure. From 2016 to 2020, a total of 860,679 inpatient ERCPs were identified. Of these procedures, 535 (0.06%) were performed in patients with CF. The mean age of patients with CF undergoing ERCP was 60.62 years, of which 48% were males and 52% were females. Patients in the CF group had a higher incidence of post-ERCP pneumothorax (0.93%) than the patients in the non-CF group (0.15%). The occurrence of other ERCP-related adverse events was similar in both groups (P>0.05). On multivariate regression analysis, patients with CF were 1.75 times more likely to develop post-ERCP infections [odds ratio (OR): 1.75; 95% CI: 1.03-2.94; P=0.035) and 7.64 times more likely to develop post-ERCP pneumothorax (OR: 7.64; 95% CI: 1.03-56.5; P=0.046) compared to patients without CF after adjusting for confounders. The groups had no significant difference in mortality, post-ERCP pancreatitis, bleeding, perforation, pneumoperitoneum, and gas embolism. There was also no significant difference in the length of stay between the study and control groups. ERCP is a safe procedure in patients with CF with a comparable risk of postprocedural complications and mortality to those who do not have cystic fibrosis. However, patients with CF may experience a higher risk of post-ERCP infections and post-ERCP pneumothorax. Further studies are needed to prospectively evaluate outcomes of ERCP in patients with CF and to determine methods of mitigating adverse events.

Discovery of GLPG2737, a Potent Type 2 Corrector of CFTR for the Treatment of Cystic Fibrosis in Combination with a Potentiator and a Type 1 Co-corrector.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. This epithelial anion channel regulates the active transport of chloride and bicarbonate ions across membranes. Mutations result in reduced surface expression of CFTR channels with impaired functionality. Correctors are small molecules that support the trafficking of CFTR to increase its membrane expression. Such correctors can have different mechanisms of action. Combinations may result in a further improved therapeutic benefit. We describe the identification and optimization of a new pyrazolol3,4-bl pyridine-6-carboxylic acid series with high potency and efficacy in rescuing CFTR from the cell surface. Investigations showed that carboxylic acid group replacement with acylsulfonamides and acylsulfonylureas improved ADMET and PK properties, leading to the discovery of the structurally novel co-corrector GLPG2737. The addition of GLPG2737 to the combination of the potentiator GLPG1837 and C1 corrector 4 led to an 8-fold increase in the F508del CFTR activity.

Chloride ion permeability of concrete containing recycled composite powder from building demolition waste

Buildings in the marine environment are vulnerable to chloride ion erosion, which threatens the service life of concrete structures. To facilitate the application of concrete containing construction demolition waste in the marine environment, recycled composite powder concrete (RCPC) was prepared using recycled composite powder as cement substitute. The chloride ion permeability of RCPC was evaluated by chloride ion diffusion test and rapid chloride ion migration test (RCM). The chloride ion permeability of RCPC continued to enhance with growing content of recycled composite powder. During the immersion age, the surface chloride ion content of the samples containing recycled composite powder increased by an average of 18.3–65.3% over the control group, with a corresponding average increase in chloride ion diffusion coefficients ranging from 17.0% to 31.5%. The chloride ion migration coefficients in the RCM test raised by 9.5–24.7%. A series of microscopic tests such as nuclear magnetic resonance (NMR), X-ray diffraction (XRD) and scanning electron microscope-energy dispersive spectrometer (SEM-EDS) suggested that the total porosity increased by 11.9–29.5% with the addition of recycled composite powder. The chloride ion diffusion coefficients exhibited a linear increase with growing total porosity and porosity of capillary pores, whereas an exponential increase with the porosity of transitional pores. The poor reactivity of the recycled composite powder resulted in a looser microstructure and weakened chloride binding capacity, and these factors boosted chloride ion transport. A chloride ion diffusion model of RCPC considering the time dependence of chloride ion transport was developed, and the reliability of the model was verified by experimental data.

Family case of cystic fibrosis

Cystic fibrosis is an autosomal recessively inherited monogenic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on the long arm of chromosome 7 (7q31.2). This mutation results in a disruption in the transport of sodium and chloride ions between intercellular fluid and the epithelial cells of the excretory ducts of the exocrine glands. This paper presents the description of a family case of cystic fibrosis involving two patients who have been under observation since birth and are sisters (patient A – 4 years 10 months, patient B – 1 year 11 months). In both patients, neonatal screening and sequential diagnosis of cystic fibrosis identified the DF508/CFTRdele2.3(21kb) mutation, the most prevalent among the Caucasian population in the Russian Federation. The primary concern in managing both patients is the correction of nutritional status and minimization of exacerbations of chronic bronchopulmonary inflammation. To determine the management strategy for these patients, a consultation was held with Dr. E.I. Kondratyeva, a leading cystic fibrosis expert and professor at the MGSC Institute, who serves as the head of the Scientific and Clinical Department of Cystic Fibrosis and the Department of Genetics of Respiratory System Diseases, an expert of the European Society for Cystic Fibrosis Committee on Diagnostics and Registry, and Deputy Chief for Scientific Work of Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region. The peculiarity of the presented clinical cases lies in the fact that within one family, with an interval of 3 years, two girls with severe disease were born. Early diagnosis was performed for both, which has allowed for the slowing down of the pathology's progression.

A Review of Durability of New and Old Concrete Joints

The purpose of this study is to explore the durability of the new and old concrete joints, including chloride ion erosion, freeze-thaw phenomena, and the influence of aggregates. Firstly, taking into account the difference in material properties between the old and new concrete, this study analyzes the chloride ion transport characteristics of the joints in detail, focusing on the key areas of the joints, that is, the areas where the old concrete may have been eroded by chloride ions. Secondly, this study explores the change in the properties of the joints under freeze-thaw conditions, and the influence of different interface treatment methods on the properties of the joints. Finally, this study examines the influence of the type and content of aggregates on the durability of the joints. Through the above research, this paper aims to provide some useful guidance and suggestions for the durability design of the old and new concrete structures.

Investigation on chloride migration behavior of metakaolin-quartz-limestone blended cementitious materials with electrochemical impedance spectroscopy method

Calcined clay and limestone powder composites offer a viable solution for reducing carbon emissions in building materials by allowing significant cement replacement. However, there is a need for further investigation into their impact on durability, especially for low-grade clays. In this study, different ratios of metakaolin and quartz powder are utilized to simulate various grades of calcined clay, while limestone powder is incorporated as a partial cement substitute. Initially, the influence of metakaolin content on rapid chloride migration was analyzed. Subsequently, various analytical techniques such as free water content, Mercury Intrusion Porosimetry (MIP), X-ray diffraction (XRD)/Rietveld method, and electrochemical impedance spectroscopy (EIS) test were employed to investigate the effects of metakaolin contents on the pore structure, phase assemblage, and electrochemical parameters of the blended cementitious system. The relationship between chloride migration coefficient and free water content, critical pore size, and impedance parameters was established to determine the key indicators for chloride migration. The study revealed that systems with partial metakaolin content demonstrate improved chloride resistance in the blended system, which could be predicted using Rct1 from the EIS test. Furthermore, the inclusion of metakaolin and limestone powder facilitated the formation of Monocarboaluminate (Mc) and Hemicarboaluminate (Hc), leading to the refinement of the pore structure and inhibition of chloride transport within the blended material. This study indicates the potential of low-grade calcined clay to enhance the overall durability of the blended cementitious system while contributing to carbon emissions reduction.

The α-7 Nicotinic Receptor Positive Allosteric Modulator Alleviates Lipopolysaccharide Induced Depressive-like Behavior by Regulating Microglial Function, Trophic Factor, and Chloride Transporters in Mice.

Neuroinflammation contributes to the pathophysiology of major depressive disorder (MDD) by inducing neuronal excitability via dysregulation of microglial brain-derived neurotrophic factor (BDNF), Na-K-Cl cotransporter-1 (NKCC1), and K-Cl cotransporter-2 (KCC2) due to activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling. Allosteric modulation of α7 nAChRs has not been investigated on BDNF, KCC2, and NKCC1 during LPS-induced depressive-like behavior. Therefore, we examined the effects of PNU120596, an α7 nAChR positive allosteric modulator, on the expression of BDNF, KCC2, and NKCC1 in the hippocampus and prefrontal cortex using Western blot analysis, immunofluorescence assay, and real-time polymerase chain reaction. The effects of ANA12, a TrkB receptor antagonist, on LPS-induced cognitive deficit and depressive-like behaviors were determined using the Y-maze, tail suspension test (TST), and forced swim test (FST). Pharmacological interactions between PNU120596 and ANA12 were also examined. Experiments were conducted in male C57BL/6J mice. LPS administration (1 mg/kg) resulted in increased expression of BDNF and the NKCC1/KCC2 ratio and decreased expression of KCC2 in the hippocampus and prefrontal cortex. PNU120596 pretreatment (4 mg/kg) attenuated the LPS-induced increase in the expression of BDNF and NKCC1/KCC2 ratio and the reduction in KCC2 expression in these brain regions. In addition, ANA12 (0.25 or 0.50 mg/kg) reduced the LPS-induced cognitive deficit and depressive-like behaviors measured by a reduced spontaneous alternation in the Y-maze and increased immobility duration in TST and FST. Coadministration of PNU120596 (1 mg/kg) and ANA12 (0.25 mg/kg) prevented the LPS-induced cognitive deficit and depressive-like behaviors. Overall, PNU120596 prevented the LPS-induced depressive-like behavior by likely decreasing neuronal excitability via targeting microglial α7 nAChR in the hippocampus and prefrontal cortex.