Photoluminescent Nanoparticles for Chemical and Biological Analysis and Imaging.

Research related to the development and application of luminescent nanoparticles (LNPs) for chemical and biological analysis and imaging is flourishing. Novel materials and new applications continue to be reported after two decades of research. This review provides a comprehensive and heuristic overview of this field. It is targeted to both newcomers and experts who are interested in a critical assessment of LNP materials, their properties, strengths and weaknesses, and prospective applications. Numerous LNP materials are cataloged by fundamental descriptions of their chemical identities and physical morphology, quantitative photoluminescence (PL) properties, PL mechanisms, and surface chemistry. These materials include various semiconductor quantum dots, carbon nanotubes, graphene derivatives, carbon dots, nanodiamonds, luminescent metal nanoclusters, lanthanide-doped upconversion nanoparticles and downshifting nanoparticles, triplet-triplet annihilation nanoparticles, persistent-luminescence nanoparticles, conjugated polymer nanoparticles and semiconducting polymer dots, multi-nanoparticle assemblies, and doped and labeled nanoparticles, including but not limited to those based on polymers and silica. As an exercise in the critical assessment of LNP properties, these materials are ranked by several application-related functional criteria. Additional sections highlight recent examples of advances in chemical and biological analysis, point-of-care diagnostics, and cellular, tissue, and in vivo imaging and theranostics. These examples are drawn from the recent literature and organized by both LNP material and the particular properties that are leveraged to an advantage. Finally, a perspective on what comes next for the field is offered.

Dextran-Functionalized Semiconductor Quantum Dot Bioconjugates for Bioanalysis and Imaging.

The prerequisites for maximizing the advantageous optical properties of colloidal semiconductor quantum dots (QDs) in biological applications are effective surface functionalization and bioconjugation strategies. Functionalization with dextran has been highly successful with some nanoparticle materials, but has had very limited application with QDs. Here, we report the preparation, characterization, and proof-of-concept applications of dextran-functionalized QDs. Multiple approaches to dextran ligands were evaluated, including performance with respect to colloidal stability across a range of pH, nonspecific binding with proteins and cells, and microinjection into cells and viability assays. Multiple bioconjugation strategies were demonstrated and applied, including covalent coupling to develop a simple pH sensor, binding of polyhistidine-tagged peptides to the QD for energy transfer-based proteolytic activity assays, and binding with tetrameric antibody complexes (TACs) to enable a sandwich immunoassay and cell immunolabeling and imaging. Our results show that dextran ligands are highly promising for the functionalization of QDs, and that the design of the ligands is tailorable to help optimally meet the requirements of applications.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead.

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35-56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Polyacrylamide gel electrophoresis of semiconductor quantum dots and their bioconjugates: materials characterization and physical insights from spectrofluorimetric detection.

Colloidal semiconductor quantum dot (QD) nanocrystals have ideal fluorescence properties for bioanalysis and bioimaging, but these materials must be functionalized with an inorganic shell, organic ligand or polymer coating, and conjugated with biomolecules to be useful in such applications. Several different analytical techniques are used to characterize QDs and their multiple layers of functionalization. Here, we revisit poly(acrylamide) gel electrophoresis (PAGE), which has been scarcely used for the characterization of QDs and their bioconjugates in deference to the routine use of agarose gel electrophoresis. We implemented PAGE in a novel "stubby" capillary format with spectrofluorimetric detection, the combination of which enabled more rapid and more detailed characterization of QDs than was possible with both poly(acrylamide) and agarose slab gels. Correlations between the peak photoluminescence (PL) emission wavelength and electropherogram peaks, especially when combined with Ferguson analysis, provided new and significant insight into the key factors that determine the electrophoretic mobility of QDs, and helped to resolve heterogeneity and sub-populations in ensembles of QDs. The method was useful for characterization of the inorganic core/shell nanocrystals, their organic ligand and polymer coatings, and their final bioconjugates, the latter of which were in the form of peptide and protein conjugates. With further development and optimization, we anticipate that capillary PAGE with spectrofluorimetric detection will become a valuable addition to the toolbox of characterization techniques suitable for QDs, their bioconjugates, and other nanoparticle materials as well.

Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model.

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Germanium Silicon Alloy Anode Material Capable of Tunable Overpotential by Nanoscale Si Segregation.

We developed the novel electrode that enables fine control of overpotential by exploiting surface segregation that is the enrichment of one component at the surface of binary alloy. To realize this approach, we controlled the proportion of Si with low Li diffusivity at the surface by annealing the SiGe nanowire in H2 environment at various temperatures. The resulting SiGe nanowires annealed at 850 °C exhibited high reversible capacity (>1031 mA·h·g(-1)), and long cycle life (400 cycles) with high capacity retention (89.0%) at 0.2 C. This superior battery performance is attributed to the remaining unlithiated part acting as support frame to prevent pulverization of anode material, which results from the fine-tuning of overpotential by controlling the degree of Si segregation.

Toxicokinetics of paraquat in Korean patients with acute poisoning.

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1±6.8 h. Cmax and AUCinf were 20.8±25.7 mg/l and 172.5±160.3 h·mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9±61.3 l/kg and 173.4±111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Quantum dot-based multidonor concentric FRET system and its application to biosensing using an excitation ratio.

A plethora of semiconductor quantum dot (QD)-based probes that rely on Förster resonance energy transfer (FRET) have been developed for the optical detection of a wide array of biological targets. To date, the vast majority of these probes have utilized one-step energy transfer between individual donor-acceptor pairs. Here, we report a new multidonor concentric FRET configuration that comprised two fluorescent dyes assembled around a central CdSeS/ZnS QD through peptide linkers. One of these dyes, either Alexa Fluor 555 (A555) or Alexa Fluor 647 (A647), served as an acceptor for both the central QD and the other coassembled dye, Alexa Fluor 488 (A488). The unresolved emission between the A488 and the QD precluded a standard analysis of FRET efficiency from quenching of donor emission intensity or decay time, instead necessitating an analysis of the two energy transfer pathways from deconvolved excitation spectra. When A647 was the terminal acceptor, both the QD-to-A647 and A488-to-A647 energy transfer pathways could be interrogated with blue light, but only the former could be interrogated with violet light. The different degrees of A647 sensitization between these two excitation wavelengths was a predictable function of the above energy transfer efficiencies and dye stoichiometry, and was exploited for quantitative bioanalysis through an excitation ratio, which is in contrast to the conventional use of an emission ratio with FRET-based probes. Detection of the activity of nanomolar concentrations of trypsin, a model protease that hydrolyzed the A488-labeled peptide linker, was demonstrated using both a fluorescence plate reader and a low-cost, compact device that used two low-power light-emitting diodes (LEDs) as excitation sources and a silicon photodiode to detect A647 emission. This multidonor concentric FRET configuration represents a new modality for ratiometric biosensing with QDs and is potentially useful for portable in vitro diagnostics.

Catalyst-free direct growth of a single to a few layers of graphene on a germanium nanowire for the anode material of a lithium battery.

Direct growth of a single to a few layers of graphene on a germanium nanowire (Gr/Ge NW; see picture) was achieved by a metal-catalyst-free chemical vapor deposition (CVD) process. The Gr/Ge NW was used as anode in a lithium ion battery. This material has a specific capacity of 1059 mA h g(-1) at 4.0 C, a long cycle life over 200 cycles, and a high capacity retention of 90%.

Preparation and Characterization of Quantum Dot-Peptide Conjugates Based on Polyhistidine Tags.

Quantum dots (QDs) offer bright and robust photoluminescence among several other advantages in comparison to fluorescent dyes. In order to leverage the advantageous properties of QDs for applications in bioanalysis and imaging, simple and reliable methods for bioconjugation are required. One such method for conjugating peptides to QDs is the use of polyhistidine tags, which spontaneously bind to the surface of QDs. We describe protocols for assembling polyhistidine-tagged peptides to QDs and for characterizing the resultant QD-peptide conjugates. The latter include both electrophoretic and FRET-based protocols for confirming successful peptide assembly, estimating the maximum peptide loading capacity, and measuring the assembly kinetics. Sensors for protease activity and intracellular delivery are briefly noted as prospective applications of QD-peptide conjugates.

Anti-Inflammatory Effect of Adipose-Derived Stromal Vascular Fraction on Osteoarthritic Temporomandibular Joint Synoviocytes.

BACKGROUND: Osteoarthritis (OA) in the temporomandibular joint (TMJ) in the TMJ (TMJ-OA) is difficult to treat, and new alternative treatments are needed. Recently, adipose-derived stem cells (ASCs) have been introduced as a promising cell source because of their anti-inflammatory effects. However, the cost and availability of these cells limited broader applications of stem cell therapy. Thus, Thus, stromal vascular fraction (SVF) containing sufficient amount of ASCs at low cost can be an alternative. In this study, we aimed to demonstrate the use of uncultured, optimally isolated SVF for the treatment of TMJ-OA. METHODS: First, we optimized the method of isolation to harvest high-quality SVFs with a large yield of ASCs. Then, we analyzed the quantity of ASCs in the SVF and performed characterization of stem cell homology. Subsequently, to evaluate the anti-inflammatory effect of high-quality SVF, an in vitro study was performed to assess the expression patterns of inflammatory cytokines including prostaglandin E2 (PGE2), IL-6, and CXCL8/IL-8, COX2, TNF, IFN, CCL2/MCP-1 and CCL5/RANTES in co-culture with synoviocytes derived from the synovial fluid in the TMJ-OA patients. RESULTS: The SVF containing approximately 32% ASCs was isolated via the our optimized isolation method. The SVF significantly down-regulated certain inflammatory cytokines such as PGE2, CXCL8/IL-8 in TMJ-OA tissue-derived synoviocytes. CONCLUSION: Although further study is needed, our study suggests that transplantation of adipose tissue-derived SVF cells might be a feasible and a novel therapeutic option for TMJ-OA in the future.

Fully Self-Assembled Silica Nanoparticle-Semiconductor Quantum Dot Supra-Nanoparticles and Immunoconjugates for Enhanced Cellular Imaging by Microscopy and Smartphone Camera.

There is a growing need for brighter luminescent materials to improve the detection and imaging of biomarkers. Relevant contexts include low-abundance biomarkers and technology-limited applications, where an example of the latter is the emerging use of smartphones and other nonoptimal but low-cost and portable devices for point-of-care diagnostics. One approach to achieving brighter luminescent materials is incorporating multiple copies of a luminescent material into a larger supra-nanoparticle (supra-NP) assembly. Here, we present a facile method for the preparation and immunoconjugation of supra-NP assemblies (SiO2@QDs) that comprised many quantum dots (QDs) around a central silica nanoparticle (SiO2 NP). The assembly was entirely driven by spontaneous affinity interactions between the constituent materials, which included imidazoline-functionalized silica nanoparticles, ligand-coated QDs, imidazole-functionalized dextran, and tetrameric antibody complexes (TACs). The physical and optical properties of the SiO2@QDs were characterized at both the ensemble and single-particle levels. Notably, the optical properties of the QDs were preserved upon assembly into supra-NPs, and single SiO2@QDs were approximately an order of magnitude brighter than single QDs and nonblinking. In proof-of-concept applications, including selective immunolabeling of breast cancer cells, the SiO2@QDs provided higher sensitivity and superior signal-to-background ratios whether using research-grade fluorescence microscopy or smartphone-based imaging. Overall, the SiO2@QDs are promising materials for enhanced bioanalysis and imaging.

Affinity Immobilization of Semiconductor Quantum Dots and Metal Nanoparticles on Cellulose Paper Substrates.

Colloidal semiconductor quantum dots (QDs), metal nanoparticles, and cellulose paper are materials with numerous applications in bioanalysis and beyond. The functional properties of QDs and metal NPs are substantially different than those of cellulose, such that their integration with cellulose paper is potentially enabling for many applications. Here, we characterize and evaluate multiple chemistries that modify cellulose paper substrates for the affinity-based immobilization of QDs, gold nanoparticles (Au NPs), and platinum nanoparticles (Pt NPs). These chemistries include grafting of cellulose fibers with imidazole and dithiol groups, as well as the aminosilanization of cellulose fibers (both with and without subsequent grafting with dithiol groups). Cellulose modifications and nanoparticle immobilization are characterized by multiple techniques, including, but not limited to, X-ray photoelectron spectroscopy, scanning electron microscopy, and optical imaging, extinction, and fluorescence measurements. We demonstrate the on-paper immobilization of color-tuned mixtures of QDs, on-paper patterning of QDs by microcontact printing, and post-immobilization enhancement of energy transfer and model assays of protease activity. The robustness of QD photoluminescence is also evaluated between immobilization chemistries. Paper-immobilized Au NPs and Pt NPs are evaluated as potential substrates for SERS and as supported catalysts for a model decolorization reaction. Our cumulative results indicate that there may not be a one-size-fits-all immobilization chemistry. Instead, the immobilization chemistry should be tailored and optimized for the downstream application.

Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors.

BACKGROUND: Adipose-derived stem cells (ADSC) have wound-healing and antioxidant effects on human skin via secretion of growth factors and activation of dermal fibroblasts. OBJECTIVE: Paracrine mechanism reducing ultraviolet-B (UVB)-induced wrinkles by ADSC is investigated in this study. METHODS AND RESULTS: Wrinkles were induced by an eight-week UVB irradiation, and were significantly improved by the subcutaneous injection of ADSC in hairless mice. In a replica analysis, parameters involving wrinkles were improved with mid-level and high doses of ADSC (1x10(4) and 1x10(5) cells). Dermal thickness and collagen contents in the dermis also were increased in the ADSC-injected groups. To characterize the paracrine mechanism involving the antiwrinkle effect of ADSC, a conditioned medium of ADSC (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB irradiation reduced the proliferation of HDF, but this was reversed by the pretreatment of ADSC-CM in a dose-dependent manner. In a cell cycle analysis, ADSC-CM decreased the UVB-induced apoptotic cell death, which was demonstrated by the reduced sub-G1 phase of HDF. In addition, the ADSC-CM increased the protein expression of collagen type I and decreased the protein level of matrix metalloproteinase 1 in HDF, which may account for the increased collagen contents in the dermis. CONCLUSIONS: Collectively, these results indicate that the ADSC and its secretory factors are effective for UVB-induced wrinkles, and the antiwrinkle effect is mainly mediated by reducing UVB-induced apoptosis and stimulating collagen synthesis of HDF.

Concentric FRET: a review of the emerging concept, theory, and applications.

Concentric Förster resonance energy transfer (cFRET) is an emerging concept for single-vector multiplexed bioanalysis and imaging. It features a network of competitive and sequential energy transfer pathways, which, to date, has been assembled with a central semiconductor quantum dot (QD) and biomolecular linkers to multiple copies of multiple types of concentrically-arranged fluorescent dyes. In this review, we provide a first-hand account of the concept and development of cFRET, starting from its place in the broader context of FRET probes and assemblies. Topics of discussion include materials for cFRET, with a focus on the enabling properties of QDs and the ideal properties of nominal acceptor dyes; characterization and analysis of cFRET configurations via photoluminescence intensity, emission ratio, lifetime, and photobleaching measurements; semi-empirical modeling to determine the rates and efficiencies of competitive and sequential FRET pathways from overall quenching efficiencies; and archetypical examples of cFRET configurations and their application in bioanalysis and imaging. Most of the latter examples demonstrate multiplexed detection of protease activity or nucleic acid targets. Examples of atypical and cFRET-like configurations are also discussed, including those that utilize time-gated FRET relays and charge-transfer quenching. We conclude with a perspective on challenges and directions for future research with cFRET. Although still emerging as a method, many exciting opportunities in bioanalysis, imaging, and beyond are envisioned for cFRET.

Evidence supporting antioxidant action of adipose-derived stem cells: protection of human dermal fibroblasts from oxidative stress.

BACKGROUND: Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue, adipose-derived stem cells (ADSCs), produced soluble factors and they exhibit diverse pharmacological effects in skin biology. OBJECTIVE: The present study examines the protective effect of ADSCs for human dermal fibroblasts (HDFs) through anti-oxidation in a tert-butyl hydroperoxide (tbOOH) induced oxidative injury model. METHODS AND RESULTS: The conditioned medium of ADSCs (ADSC-CM) was harvested and tested for antioxidant action. ADSC-CM had an antioxidant effect as potent as 100 microM ascorbic acid and various antioxidant proteins were detected in ADSC-CM by proteomic analysis. Morphological change and cell survival assay revealed that incubation with ADSC-CM aided HDFs to resist free radicals induced by tbOOH. In addition, activities of superoxide dismutase and glutathione peroxidase were enhanced in the ADSC-CM treated HDFs which confirmed the study hypothesis that ADSCs protect HDFs through antioxidant action. In a cell cycle analysis, ADSC-CM treatment reversed the apoptotic cell death induced by tbOOH and caused a decrease of sub-G1 cells with respect to untreated cells. The anti-apoptotic effect of ADSC-CM was also reproduced by caspase-3 activity assay. CONCLUSION: These results suggest that ADSCs have potent antioxidant activity and protect HDFs from oxidative injury by decreasing apoptotic cells. Therefore, ADSCs and ADSC-CM are good candidates for control and prevention of skin damage from free radicals in various skin conditions.

A Novel Secretory Vesicle from Deer Antlerogenic Mesenchymal Stem Cell-Conditioned Media (DaMSC-CM) Promotes Tissue Regeneration.

Multipotent stem cells have the capacity to generate terminally differentiated cell types of each lineage; thus, they have great therapeutic potential for a wide variety of diseases. The most widely available stem cells are derived from human tissues, and their use for therapeutic application is limited by their high cost and low productivity. Herein, we report that conditioned media of mesenchymal stem cells (MSCs) isolated from deer antlers enhanced tissue regeneration through paracrine action via a combination of secreted growth factors and cytokines. Notably, DaMSC-conditioned media (DaMSC-CM) enhanced hair regeneration by activating the Wnt signaling pathway. In addition, DaMSC-CM had regenerative potential in damaged skin tissue through induction of skin regeneration-related genes. Remarkably, we identified round vesicles derived from DaMSC-CM, with an average diameter of ~120 nm that were associated with hair follicle formation, suggesting that secretory vesicles may act as paracrine mediators for modulation of local cellular responses. In addition, these secretory vesicles could regulate the expression of Wnt-3a, Wnt-10b, and lymphoid enhancer-binding factor-1 (LEF-1), which are related to tissue renewal. Thus, our findings demonstrate that the use of DaMSC-CM as a unique natural model for rapid and complete tissue regeneration has possible application for therapeutic development.

Effects of Panax ginseng C.A. Meyer extract on the offspring of adult mice with maternal immune activation.

To understand maternal immune activation (MIA) during prenatal development, the synthetic double­stranded RNA polyriboinosinic­polyribocytidylic acid [poly(I:C)] has been widely used in animal models to induce behavioral deficits similar to those in schizophrenia and other psychotic disorders. Panax ginseng C.A. Meyer (PG) extract is widely used to treat various kinds of nervous system disorders in Asia particularly China and Korea. The present study aimed to examine the effects of PG extract on MIA offspring using behavioral activity tests and protein expression analyses. Pregnant mice were exposed to poly(I:C) (5 mg/kg) or vehicle treatment on gestation day 9, and the resulting MIA offspring were subjected to vehicle or PG (300 mg/kg) treatment. In the acoustic startle response test, MIA­induced sensorimotor gating deficit was ameliorated by PG. The majority of behavioral parameters measured in the social interaction (non­aggressive or/and aggressive pattern), open field (number/duration of behavior) and forced swimming test (immobility behavior) were significantly altered in the MIA offspring. Western blot and immunohistochemical analyses of the medial prefrontal cortex indicated that the expression levels of certain neurodevelopmental proteins, including dihydropyrimidinase­related 2, LIM and SH3 domain 1, neurofilament medium, and discs large homolog 4, were decreased in the untreated MIA offspring, whereas PG treatment improved behavioral impairments and increased neurodevelopmental protein expression in MIA offspring. These results suggested that PG may be useful in neurodevelopmental disorder therapy, including psychiatric disorders such as schizophrenia, owing to its antipsychotic effects.

Antinociceptive effect of Valeriana fauriei regulates BDNF signaling in an animal model of fibromyalgia.

The genus Valeriana has been widely used in popular medicine for centuries, to treat sleep disorders, anxiety, epilepsy and insomnia. Recent studies have focused on the novel pharmacological effects of Valeriana fauriei Briq. (VF) species. Previous studies have attempted to determine the pharmacological functions of Valeriana in various human diseases, particularly with regards to its neuroprotective effects, and its ability to reduce pain and stress. The present study constructed an animal model of fibromyalgia (FM), which was induced by intermittent cold stress with slight modification. Subsequently, the study aimed to determine whether VF exerts antinociceptive effects on the FM­like model following oral administration of VF extracts. The effects of VF extracts on the FM model were investigated by analyzing behavioral activity, including pain, and detecting protein expression. In the behavioral analysis, the results of a nociception assay indicated that the pain threshold was significantly decreased in the FM group. Subsequently, western blotting and immunohistochemical analyses of the hippocampus demonstrated that the protein expression levels of brain­derived neurotrophic factor (BDNF) and phosphorylated­cAMP response element­binding protein were downregulated in the FM group. Conversely, VF restored these levels. These results suggested that the effects of VF extract on a model of FM may be associated with its modulatory effects on the BDNF signaling pathway in the hippocampus and medial prefrontal cortex. In conclusion, the mechanism underlying the protective effects of VF as a therapeutic agent against FM may involve the BDNF signaling pathway.

Effects of Tianeptine on Adult Rats Following Prenatal Stress.

OBJECTIVE: Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats. METHODS: In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies. RESULTS: Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased. CONCLUSION: Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.