Histochemistry evaluation of the oxidative stress and the antioxidant status in Cu-supplemented cattle

The aim of this paper is to evaluate at a histopathological level the effect of the most commonly used copper (Cu) supplementation (15 mg/kg dry matter (DM)) in the liver of intensively reared beef cattle. This was done by a histochemistry evaluation of (i) the antioxidant capacity in the liver – by the determination of metallothioneins (MT) and superoxide dismutase (SOD) expression – as well as (ii) the possible induction of oxidative damage – by the determination of inducible nitric oxide synthase (iNOS), nitrotyrosine (NITT), malondialdehyde (MDA) and 8-oxoguanine (8-oxo) – that (iii) could increase apoptotic cell death – determined by cytochrome-c (cyto-c), caspase 1 (casp1) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Liver samples from Cu-supplemented (15 mg Cu sulphate/kg DM, n = 5) and non-supplemented calves (n = 5) that form part of other experiments to evaluate Cu status were collected at slaughter and processed for immunohistochemistry and TUNEL. MT expression was diffuse and SOD showed slight changes although without statistical significance. iNOS and NITT positive (+) cells significantly increased, mainly around the central veins in the animals from the Cu-supplemented group, whereas no differences were appreciated for the rest of the oxidative stress and apoptosis markers. Under the conditions of this study, which are the conditions of the cattle raised in intensive systems in NW Spain and also many European countries, routinely Cu supplementation increased the risk of the animals to undergo subclinical Cu toxicity, with no significant changes in the Cu storage capacity and the antioxidant defensive system evaluated by MT and SOD expression, but with a significant and important increase of oxidative damage measured by iNOS and NITT. The results of this study indicated that iNOS and NITT could be used as early markers of initial pathological changes in the liver caused by Cu supplementation in cattle, although more studies in cattle under different levels of Cu supplementation are needed.     

Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: Influence of exercise training on antioxidant defense system

This study investigated the onset of age-related changes in the myocardial antioxidant defense system (ADS) and the vulnerability of the myocardium to oxidative stress following exercise training. Few studies have investigated the influence of the most prevalent life-prolonging strategy physical exercise, on the age-dependent alterations in the myocardial antioxidant enzyme system of female rats at mid age and to determine whether exercise-induced ADS could attenuate lipid peroxidation. Two age groups young (3 months old) and mid age (12 months old) Wistar strain female albino rats were given chronic exercise training for a period of 12 weeks. We found a striking decrease (p < 0.01) in the activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in the myocardium of mid aged rats when compared to young rats by 36, 50 and 29%, respectively, suggesting the onset of age-dependent decrease in the myocardial ADS. A similar age-related decrease (p < 0.01) was observed in the reduced glutathione (GSH) content (36%). Despite the reduction in ADS, lipid peroxidation (LPO) (20%) was also decreased. In contrast, exercise training significantly elevated (p < 0.01) these antioxidant enzyme activities and the content of GSH. The increase in SOD and CAT activities were more pronounced in the mid aged rats when compared to younger rats, but increased the level of lipid peroxidation to higher levels in the mid-age group following the training regimen. The findings of the present study suggest that, although the activity levels of the myocardial antioxidant enzymes were elevated with the 12 weeks of exercise training, the changes were not sufficient enough in attenuating oxidative stress in the myocardium of female rats during this short period of exercise training.     

Eriodictyol alleviates lipopolysaccharide-triggered oxidative stress and synaptic dysfunctions in BV-2 microglial cells and mouse brain

Oxidative stress takes part in the development of the neurodegenerative disease. Eriodictyol, a flavonoid, commonly presents in citrus fruits, which was well-known for its various bioactivities. The purpose of this study was to investigate the neuroprotective effects of eriodictyol on lipopolysaccharide (LPS)-induced neuroinflammation, oxidative stress, synaptic dysfunctions, and the potential mechanisms involved. We found that eriodictyol explicitly restored LPS-triggered the decrease of cell viability and the mitochondrial potential as well as inflammation responses via mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) pathways regulated by reactive oxygen species (ROS). Besides, eriodictyol alleviated LPS-induced oxidative stress via NF-E2-Related factor2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway in vivo and in vitro. Furthermore, eriodictyol reduced LPS-elicited synaptic dysfunctions via increasing the expression of silent information regulator 1 (Sirt1). Overall, eriodictyol protects LPS-triggered oxidative stress, neuroinflammation, and synaptic dysfunctions partially through MAPKs, NF-κB mediated by ROS, Sirt1, and Nrf2/Keap1 signal pathways, which further supports that eriodictyol is a potentially nutritional preventive strategy for oxidative stress-related neurodegenerative diseases.     

Effects of taurine on oxidative stress parameters and chromium levels altered by acute hexavalent chromium exposure in Mice Kidney tissue

The kidney has been regarded as a critical organ of toxicity induced by acute exposure to hexavalent chromium [Cr(VI)] compounds. Reactive intermediates and free radicals generated during reduction process might be responsible for Cr(VI) toxicity. In this study, the effects of pretreatment or posttreatment of taurine on Cr(VI)-induced oxidative stress and chromium accumulation in kidney tissue of Swiss albino mice were investigated. Single intraperitoneal (ip) potassium dichromate treatment (20 mgCr/kg), as Cr(VI) compound, significantly elevated the level of lipid peroxidation as compared with the control group (p<0.05). This was accompanied by significant decreases in nonprotein sulfhydryls (NPSH) level, superoxide dismutase (SOD), and catalase (CAT) enzyme activities as well as a significant chromium accumulation (p<0.05). Taurine administration (1 g/kg, ip) before or after Cr(VI) exposure resulted in reduction of lipid peroxidation levels and improvement in SOD enzyme activity (p<0.05). On the other hand, administration of the antioxidant before Cr(VI) exposure restored the NPSH level and CAT enzyme activity and also reduced tissue chromium levels (p<0.05), whereas postreatment had only slight effects on these parameters. In view of the results, taurine seems to exert some beneficial effects against Cr(VI)-induced oxidative stress and chromium accumulation in mice kidney tissue.     

Swim training attenuates oxidative damage and promotes neuroprotection in cerebral cortical slices submitted to oxygen glucose deprivation

Although it is well known that regular exercise may promote neuroprotection, the mechanisms underlying this effect are still not fully understood. We investigated if swim training promotes neuroprotection by potentiating antioxidant pathways, thereby decreasing the effects of oxidative stress on glutamate and nitric oxide release. Male Wistar rats (n=36) were evenly randomized into a trained group (TRA) (5 days/week, 8 weeks, 30 min) and a sedentary group (SED). Forty‐eight hours after the last session of exercise, animals were killed and brain was collected for in vitro ischemia. Cortical slices were divided into two groups: a group in which oxidative stress was induced by oxygen and glucose deprivation (OGD), and a group of non‐deprived controls (nOGD). Interestingly, exercise by itself increased superoxide dismutase activity (nOGD, SED vs. TRA animals) with no effect on pro‐oxidative markers. In fact, TRA‐OGD slices showed lowered levels of lactate dehydrogenase when compared with SED‐OGD controls, reinforcing the idea that exercise affords a neuroprotective effect. We also demonstrated that exercise decreased glutamate and nitrite release as well as lipid membrane damage in the OGD cortical slices. Our data suggest that under conditions of metabolic stress, swim training prevents oxidative damage caused by glutamate and nitric oxide release.     

Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase

Nitroalkene derivative of oleic acid (OA-NO₂), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO₂ attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO₂ in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO₂ (1.25?μM, 45?min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO₂ promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO₂ inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22^phox up-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO₂ reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.     

Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats

BACKGROUNDChromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats.METHODSGC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively.RESULTSTwenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H₂O₂) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers.CONCLUSIONConclusively, REO had a potential antioxidant capacity in ameliorating K₂Cr₂O₇-induced nephrotoxicity, especially in the protection group.     

Vitamin C and E combination modulates oxidative stress induced by X‐ray in blood of smoker and nonsmoker radiology technicians

X‐ray radiation is detrimental to human cells and may lead to development of life‐threatening diseases. Cigarette smoke contains about 500 chemicals that include organic and oxidant compounds whereas vitamin C and E (VCE) have scavenger effects on the compounds. We investigated effects of VCE administration on X‐ray‐induced oxidative toxicity in blood of smoker and nonsmoker X‐ray technicians. Twenty technicians and 30 healthy age‐matched subjects control were used in the study. Ten of the X‐ray technicians and 15 of the control were smokers. Blood samples were taken from the control. Oral vitamin C (500 mg) and vitamin E (150 mg) were daily supplemented to the smoker and nonsmoker X‐ray technicians for 5 weeks. Blood samples were taken from the X‐ray technicians after and before 5 weeks. Plasma and erythrocytes lipid peroxidation (LP), reduced glutathione (GSH) levels, erythrocytes glutathione peroxidase (GSH‐Px), and plasma antioxidant vitamin concentrations were investigated in control and X‐ray technicians with smoker and nonsmoker. Plasma and erythrocytes LP levels were higher in the total X‐ray group and smoker X‐ray group than in control and nonsmoker X‐ray group, respectively although the LP level was decreased by the VCE treatment. The plasma vitamin C, vitamin A, vitamin E, and β‐carotene concentrations were lower in the X‐ray group than in control although their concentrations were increased by the treatment. The erythrocytes GSH level and GSH‐Px activity were found to be higher in the treatment group than in the X‐ray group. Plasma GSH level was not found to be different in all group. Reactive oxygen species may play role in the mechanism that has been proposed to explain the biological side effect of X‐ray radiation and smoke. VCE prevents the smoke and X‐ray‐induced oxidative stress to strengthen antioxidant vitamin concentrations in the blood of the technicians. Copyright © 2009 John Wiley & Sons, Ltd.     

Validation of organotypical hippocampal slice cultures as an ex vivo model of brain ischemia: different roles of NMDA receptors in cell death signalling after exposure to NMDA or oxygen and glucose deprivation

N-Methyl-D-aspartate receptors (NMDARs) are essential mediators of synaptic plasticity under normal physiological conditions. During brain ischemia, these receptors are excessively activated due to glutamate overflow and mediate excitotoxic cell death. Although organotypical hippocampal slice cultures are widely used to study brain ischemia in vitro by induction of oxygen and glucose deprivation (OGD), there is scant data regarding expression and functionality of NMDARs in such slice cultures. Here, we have evaluated the contribution of NMDARs in mediating excitotoxic cell death after exposure to NMDA or OGD in organotypical hippocampal slice cultures after 14 days in vitro (DIV14). We found that all NMDAR subunits were expressed at DIV14. The NMDARs were functional and contributed to cell death, as evidenced by use of the NMDAR antagonist MK-801 (dizocilpine). Excitotoxic cell death induced by NMDA could be fully antagonized by 10 μM MK-801, a dose that offered only partial protection against OGD-induced cell death. Very high concentrations of MK-801 (50–100 μM) were required to counteract cell death at long delays (48–72 h) after OGD. The relative high dose of MK-801 needed for long-term protection after OGD could not be attributed to down-regulation of NMDARs at the gene expression level. Our data indicate that NMDAR signaling is just one of several mechanisms underlying ischemic cell death and that prospective cytoprotective therapies must be directed to multiple targets.     

Age-related effect induced by oxidative stress on the cerebral glutathione system

In the forebrain from male Wistar rats aged 5, 15 and 25 months, age-related putative alterations in the glutathione system (reduced and oxidized glutathione; redox index) were chronically induced by the administration in drinking water of free radical generators (hydrogen peroxide, ferrous chloride) or of inhibitors of endogenous free radical defenses (diethyl-dithio-carbamate, an inhibitor of superoxide dismutase activity). In hydrogen peroxide administered rats, both reduced glutathione and the cerebral glutathione redox index markedly declined as a function of aging, whereas oxidized glutathione consistently increased. In contrast, chronic iron intake failed to modify the reduced glutathione in forebrain from the rats of the different ages tested, whereas the oxidized glutathione was increased in the older brains. The chronic intake of diethyl-dithio-carbamate enhanced the concentrations of reduced glutathione in the forebrains from the rats of the different ages tested, the oxidized glutathione being unchanged. In 15-month-old rats submitted to chronic oxidative stress, ergot alkaloids (and particularly dihydroergocriptine) interfered with cerebral glutathione system, while papaverine was always ineffective. The comprehensive analysis of the data indicates that: (a) both the type of oxidative stress and the age of the animals modulate the cerebral responsiveness to the putative modifiers in the level of tissue free radicals; (b) aging magnifies the cerebral alterations induced by oxidative stress; the (c) cerebral glutathione system may be modified by metabolic rather than by circulatory interferences; (d) a balance between the various cerebral antioxidant defenses is present, the perturbation of an antioxidant system resulting in the compensatory modified activity of component(s) of another system.     

Loperamide‐induced cardiotoxicity in rats: Evidence from cardiac and oxidative stress biomarkers

At therapeutic dose, loperamide is a safe over‐the‐counter antidiarrheal drug but could induce cardiotoxic effect at a supratherapeutic dose. In this study, we use cardiac and oxidative biomarkers to evaluate loperamide‐induced cardiotoxicity in rats. Rats were orally gavaged with 1.5, 3, or 6 mg/kg body weight (BW) of loperamide hydrochloride for 7 days. The results after 7 days administration of loperamide, revealed dose‐dependent increase (P < 0.05) in aspartate aminotransferase, lactate dehydrogenase, creatine kinase‐MB, and serum concentration of cardiac troponin I, total homocysteine, and nitric oxide. A 50% decrease in antioxidant enzymes activity was observed at 6 mg/kg BW. Furthermore, malondialdehyde and fragmented DNA also increased significantly in the heart of the treatment groups. Loperamide provoked cardiotoxicity through oxidative stress, lipid peroxidation, and DNA fragmentation in rats. This study has provided a possible biochemical explanation for the reported cardiotoxicity induced by loperamide overdose.     

Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism

There is a correlation between oxidative stress generated by diethylnitrosamine (DEN) metabolism and liver cancer development. Quercetin is a flavonoid with anti-carcinogenic and antioxidant properties. This study demonstrates the mechanism of action for the chemopreventive effect of quercetin. A 10 mg/kg dose of quercetin produced drastic effect, when it is administrated 2 h before DEN; at 24 days post-DEN, a 70.3% and 66.2% decrease in total area and number of preneoplastic lesions were observed, respectively. At 12 h post-DEN, quercetin inhibited levels of lipid peroxidation by 40%. Quercetin increased the levels of both GSH and of total glutathione, it increased the GSH/GSSG index and it caused a rapid and simultaneous elevation in the activities of superoxide dismutase, glutathione peroxidase and catalase. In conclusion, the quercetin mechanism of action is due to promote the enzymatic and non-enzymatic antioxidant defense system during the initiation of hepatocarcinogenesis.     

Terrein reduces age‐related inflammation induced by oxidative stress through Nrf2/ERK1/2/HO‐1 signalling in aged HDF cells

This study investigated whether multiple bioactivity of terrein such as anti‐inflammatory and anti‐oxidant inhibits age‐related inflammation by promoting an antioxidant response in aged human diploid fibroblast (HDF) cells. HDF cells were cultured serially for in vitro replicative senescence. To create the ageing cell phenotype, intermediate stage (PD31) HDF cells were brought to stress‐induced premature senescence (SIPS) using hydrogen peroxide (H₂O₂). Terrein increased cell viability even with H₂O₂ stress and reduced inflammatory molecules such as intracellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), interleukin‐1beta (IL‐1β) and tumour necrosis factor‐alpha (TNF‐α). Terrein reduced also phospho‐extracellular kinase receptor1/2 (p‐EKR1/2) signalling in aged HDF cells. SIPS cells were attenuated for age‐related biological markers including reactive oxygen species (ROS), senescence associated beta‐galactosidase (SA β‐gal.) and the aforementioned inflammatory molecules. Terrein induced the induction of anti‐oxidant molecules, copper/zinc‐superoxide defence (Cu/ZnSOD), manganese superoxide dismutase (MnSOD) and heme oxygenase‐1 (HO‐1) in SIPS cells. Terrein also alleviated reactive oxygen species formation through the Nrf2/HO‐1/p‐ERK1/2 pathway in aged cells. The results indicate that terrein has an alleviative function of age‐related inflammation characterized as an anti‐oxidant. Terrein might be a useful nutraceutical compound for anti‐ageing. Copyright © 2015 John Wiley & Sons, Ltd.     

香椿子正丁醇提取物通过激活Nrf2改善高糖引起的肾小球内皮细胞氧化应激

目的探讨香椿子正丁醇提取物(n-butyl alcohol extract of toona sinensis,NBAE)对高糖引起的肾小球内皮细胞氧化应激的影响及机制。方法分别以高糖(high glucose,HG)、HG+NBAE刺激人肾小球内皮细胞,采用DCFDA法检测细胞内活性氧(reactive oxygenspecies,ROS)生成情况,Nitrate/Nitrite Colorimetric法检测细胞内NO的含量,Western blot检测Nrf2、NQO1及HO-1的蛋白表达,免疫荧光方法检测Nrf2、P47phox在细胞内的定位及表达。结果高糖刺激肾小球内皮细胞后出现氧化应激损伤,ROS升高,NO减少,p47phox表达量增高,Nrf2及下游蛋白NQO1、HO-1表达减少;NBAE可明显提高Nrf2的表达,并增加下游蛋白NQO1和HO-1的表达,从而抑制高糖导致的ROS升高,抑制p47phox的表达,并稳定NO的含量。结论NBAE通过激活Nrf2及其下游靶蛋白来改善高糖对肾小球内皮细胞造成的氧化应激损伤。     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

In vivo monitor oxidative burst induced by Cd2+ stress for the oilseed rape (Brassica napus L.) based on electrochemical microbiosensor

Introduction – Since the mechanism of Cd²⁺ stress for plants is not clear, an in vivo method to monitor Cd²⁺ stress for plants is necessary. However, oxidative burst (OB) is a signal messenger in the process of Cd²⁺ stress for plants. Objective – To establish an electrochemical method with poly‐o‐phenylenediamine and Pt microparticle modified Pt electrode (POPD–Pt‐MP–Pt) as a microbiosensor for the in vivo detection of oxidative burst induced by Cd²⁺ stress in oilseed rape (Brassica napus L.). Methodology – The optimal fabrication of POPD–Pt‐MP–Pt biosensor was achieved. Electrochemical signal was collected by amperometry. Results – After oilseed rape was exposed to 84.9 mM CdCl₂ stress, three oxidative bursts were observed in oilseed rape by amperometry at 3.3 h, 8.4 h and 13.2 h, respectively. However, there was no obvious signal observed in the controlled assay. Conclusion – This contribution presents the in vivo monitoring of the OB process induced by Cd²⁺ stress in oilseed rape by POPD–Pt‐MP–Pt microbiosensor in real‐time. The novel electrochemical microbiosensor not only facilitates the real‐time study in plant self‐defence response to the adverse environment such as Cd²⁺ stress, but also provides an effective tool for probing the self‐defence mechanism in plants. Copyright © 2009 John Wiley & Sons, Ltd.     

Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons

Postsynaptic molecules with PDZ domains (PDZ proteins) interact with various glutamate receptors and regulate their subcellular trafficking and stability. In rat neocortical development, the protein expression of AMPA-type glutamate receptor GluR1 lagged behind its mRNA expression and rather paralleled an increase in PDZ protein levels. One of the neurotrophins, brain-derived neurotrophic factor (BDNF), appeared to contribute to this process, regulating the PDZ protein expression. In neocortical cultures, BDNF treatment upregulated SAP97, GRIP1, and Pick1 PDZ proteins. Conversely, BDNF gene targeting downregulated these same PDZ molecules. The BDNF-triggered increases in PDZ proteins resulted in the elevation of their total association with the AMPA receptors GluR1 and GluR2/3, which led to the increase in AMPA receptor proteins. When Sindbis viruses carrying GluR1 or GluR2 C-terminal decoys disrupted their interactions, GluR2 C-terminal decoys inhibited both BDNF-triggered GluR1 and GluR2/3 increases, whereas GluR1 C-terminal decoys blocked only the BDNF-triggered GluR1 increase. In agreement, coexpression of SAP97 and GluR1 in nonneuronal HEK293 cells increased both proteins compared with their single transfection, implying mutual stabilization. This work reveals a novel function of BDNF in postsynaptic development by regulating the PDZ protein expression.