Oxidised LDL-lipids alter redox ratio, lipid raft formation and increase amyloid beta production by SHSY-5Y cells

Elevated cholesterol in mid-life has been associated with increased risk of dementia in later life. We have previously shown that low density lipoprotein (LDL) is more oxidised in the plasma of dementia patients although total cholesterol levels remained unchanged [1]. We have investigated the hypothesis that amyloid beta production and neurodegeneration can be driven by oxidised lipids derived from LDL following the loss of blood brain barrier integrity with ageing. Therefore, we have investigated amyloid beta formation in SHSY5Y cells treated with LDL, minimally modified (ox) LDL, and lipids extracted from both forms of LDL. LDL-treated SHSY-5Y cell viability was not significantly decreased with up to 8 μg LDL/2 × 104 cells compared to untreated cells. However, 8 μg oxLDL protein/2 × 104 cells decreased the cell viability significantly by 33.7% (P < 0.05). A more significant decrease in cell viability was observed when treating cells with extracted lipids from 8 μg of LDL (by 32.7%; P < 0.01) and oxLDL (by 41%; P < 0.01). In parallel, the ratio of reduced to oxidised GSH was decreased; GSH concentrations were significantly decreased following treatment with 0.8 μg/ml oxLD-L (7.35 ± 0.58;P < 0.01), 1.6 μg/ml (5.27 ± 0.23; P < 0.001) and 4 μg/ml (5.31 ± 0.31; P < 0.001). This decrease in redox potential was associated with an increase acid sphingomyelinase activity and lipid raft formation which could be inhibited by desipramine; SHSY5Y cells treated with oxLDL, and lipids from LDL and oxLDL for 16 h showed significantly increased acid sphingomyelinase activity (5.32 ± 0.35; P < 0.05, 5.21 ± 0.6; P < 0.05, and 5.58 ± 0.44; P < 0.01, respectively) compared to control cells (2.96 ± 0.34). As amyloid beta production is driven by the activity of beta secretase and its association with lipid rafts, we investigated whether lipids from ox-LDL can influence amyloid beta by SHSY-5Y cells in the presence of oxLDL. Using ELISA and Western blot, we confirmed that secretion of amyloid beta oligomers is increased by SHSY-5Y cells in the presence of oxLDL lipids. These data suggest a mechanism whereby LDL, and more significantly oxLDL lipids, can drive amyloid beta production and cytotoxicity in neuronal cells. [1] Li L, Willets RS, Polidori MC, Stahl W, Nelles G, Sies H, Griffiths HR. Oxidative LDL modification is increased in vascular dementia and is inversely associated with cognitive performance. Free Radic Res. 2010 Mar; 44(3): 241–8.

Reduced organic sulfur: Analysis and interaction with mercury in the aquatic environment

Reduced organic sulfur (ROS) compounds are environmentally ubiquitous and play an important role in sulfur cycling as well as in biogeochemical cycles of toxic metals, in particular mercury. Development of effective methods for analysis of ROS in environmental samples and investigations on the interactions of ROS with mercury are critical for understanding the role of ROS in mercury cycling, yet both of which are poorly studied. Covalent affinity chromatography-based methods were attempted for analysis of ROS in environmental water samples. A method was developed for analysis of environmental thiols, by preconcentration using affinity covalent chromatographic column or solid phase extraction, followed by releasing of thiols from the thiopropyl sepharose gel using TCEP and analysis using HPLC-UV or HPLC-FL. Under the optimized conditions, the detection limits of the method using HPLC-FL detection were 0.45 and 0.36 nM for Cys and GSH, respectively. Our results suggest that covalent affinity methods are efficient for thiol enrichment and interference elimination, demonstrating their promising applications in developing a sensitive, reliable, and useful technique for thiol analysis in environmental water samples. The dissolution of mercury sulfide (HgS) in the presence of ROS and dissolved organic matter (DOM) was investigated, by quantifying the effects of ROS on HgS dissolution and determining the speciation of the mercury released from ROS-induced HgS dissolution. It was observed that the presence of small ROS (e.g., Cys and GSH) and large molecule DOM, in particular at high concentrations, could significantly enhance the dissolution of HgS. The dissolved Hg during HgS dissolution determined using the conventional 0.22 μm cutoff method could include colloidal Hg (e.g., HgS colloids) and truly dissolved Hg (e.g., Hg-ROS complexes). A centrifugal filtration method (with 3 kDa MWCO) was employed to characterize the speciation and reactivity of the Hg released during ROS-enhanced HgS dissolution. The presence of small ROS could produce a considerable fraction (about 40% of total mercury in the solution) of truly dissolved mercury (< 3 kDa), probably due to the formation of Hg-Cys or Hg-GSH complexes. The truly dissolved Hg formed during GSH- or Cys-enhanced HgS dissolution was directly reducible (100% for GSH and 40% for Cys) by stannous chloride, demonstrating its potential role in Hg transformation and bioaccumulation.

Formation of Polycyclic Aromatic Hydrocarbons and Nitrogen Containing Polycyclic Aromatic Compounds in Titan's Atmosphere, the Interstellar Medium and Combustion

Several different mechanisms leading to the formation of (substituted) naphthalene and azanaphthalenes were examined using theoretical quantum chemical calculations. As a result, a series of novel synthetic routes to Polycyclic Aromatic Hydrocarbons (PAHs) and Nitrogen Containing Polycyclic Aromatic Compounds (N-PACs) have been proposed. On Earth, these aromatic compounds originate from incomplete combustion and are released into our environment, where they are known to be major pollutants, often with carcinogenic properties. In the atmosphere of a Saturn's moon Titan, these PAH and N-PACs are believed to play a critical role in organic haze formation, as well as acting as chemical precursors to biologically relevant molecules. The theoretical calculations were performed by employing the ab initio G3(MP2,CC)/B3LYP/6-311G** method to effectively probe the Potential Energy Surfaces (PES) relevant to the PAH and N-PAC formation. Following the construction of the PES, Rice-Ramsperger-Kassel-Markus (RRKM) theory was used to evaluate all unimolecular rate constants as a function of collision energy under single-collision conditions. Branching ratios were then evaluated by solving phenomenological rate expressions for the various product concentrations. The most viable pathways to PAH and N-PAC formation were found to be those where the initial attack by the ethynyl (C2H) or cyano (CN) radical toward a unsaturated hydrocarbon molecule led to the formation of an intermediate which could not effectively lose a hydrogen atom. It is not until ring cyclization has occurred, that hydrogen elimination leads to a closed shell product. By quenching the possibility of the initial hydrogen atom elimination, one of the most competitive processes preventing the PAH or N-PAC formation was avoided, and the PAH or N-PAC formation was allowed to proceed. It is concluded that these considerations should be taken into account when attempting to explore any other potential routes towards aromatic compounds in cold environments, such as on Titan or in the interstellar medium.

Paleoceanographic and paleoclimatic evolution of the Aegean Sea since the last interglacial (~130 ka BP) with special emphasis on sapropel formation

Five long piston cores collected from different subbasins of the Aegean Sea constitute the primary source of data for this PhD thesis. This study is the first to document a continuous paleoceanographic and paleoclimatic record of the Aegean Sea since the last interglacial. The chronostratigraphic reconstructions of the cored sediments based on organic carbon contents, stratigraphic position of known ash layers and oxygen isotopic curve matching collectively demonstrate the presence of sapropel S1 and MISS sapropels S3, S4 and S5 in the Aegean Sea subbasins. Generally, the organic carbon (TOC wt%) contents in sapropels range between 0.8% and 2% with highest concentrations of 9-13% in sapropels S4 and S5. Average sedimentation rates range between 4.7 and 11.8 cmlka with highest rates being observed in Euboea and North Ikaria basins (9.8 and 11.8 cm lka, respectively). The timing of the onset of sapropels S4 and S5 mostly predate those in the eastern Mediterranean with ages ranging from 106.4-105.6 and 128.6-128.4 ka BP, respectively. On the other hand, the initiation of the onset of sapropel S3 (i.e., 83.2-80.4 ka BP) seems to agree with its Mediterranean counterparts, which highlights the heterogeneity of the Aegean Sea subbasins in terms of rapid vs. lagged response to changing climatic conditions. The sapropel initiations appear to be synchronous across the Aegean Sea; whereas, the terminations display a wider temporal variability implying that the cessation of sapropels is controlled both by the amplitude of paleoclimatic changes and the physiography/location ofthe subbasins. Quantitative variations in the planktonic faunal assemblages exhibit a sequence of bioevents during the last -130,000 years which allow identification of four major biozones. The distributional patterns of the most significant taxa demonstrate similar trends among all core localities suggesting that the major changes in the planktonic foraminifera assemblages have taken place rather synchronously in the Aegean Sea. Sapropels S3, S4 and S5 were deposited under similar hydrographic conditions during which a distinct deep chlorophyll maximum (DCM) layer was established. This situation points to a stratified water column and increased export productivity during times of sapropel formation. On the other hand, the faunal contrast between Sl and older sapropels indicates that the former was developed in the absence of a DCM layer, lacking a deep phytoplankton assemblage. Under such conditions, oxygen advection via intermediate water flow must have been significantly reduced which implies significant stagnation. Sapropels are interpreted to have been deposited under normal marine conditions with temporary establishment of semi-euxinic bottom water conditions. Both marine and terrestrial organic matter contributed equally to MISS sapropels. In addition, organic carbon isotopic values across sapropels are more depleted than those in the eastern Mediterranean which, in tum, suggests enhanced riverine input during their deposition. Primary productivity calculations show that, particularly for sapropels with very high TOC values, both preservation and increased productivity are imperative in order to deposit sapropels with very high organic carbon contents (i.e., up to 13%).

Charge compensation and Ce3+ formation in trivalent doping of the CeO2(110) surface: The key role of dopant ionic radius

In this paper, we use density functional theory corrected for on-site Coulomb interactions (DFT + U) and hybrid DFT (HSE06 functional) to study the defects formed when the ceria (110) surface is doped with a series of trivalent dopants, namely, Al3+, Sc3+, Y3+, and In 3+. Using the hybrid DFT HSE06 exchange-correlation functional as a benchmark, we show that doping the (110) surface with a single trivalent ion leads to formation of a localized MCe / + O O • (M = the 3+ dopant), O- hole state, confirming the description found with DFT + U. We use DFT + U to investigate the energetics of dopant compensation through formation of the 2MCe ′ +VO ̈ defect, that is, compensation of two dopants with an oxygen vacancy. In conjunction with earlier work on La-doped CeO2, we find that the stability of the compensating anion vacancy depends on the dopant ionic radius. For Al3+, which has the smallest ionic radius, and Sc3+ and In3+, with intermediate ionic radii, formation of a compensating oxygen vacancy is stable. On the other hand, the Y3+ dopant, with an ionic radius close to that of Ce4+, shows a positive anion vacancy formation energy, as does La3+, which is larger than Ce4+ (J. Phys.: Condens. Matter 2010, 20, 135004). When considering the resulting electronic structure, in Al3+ doping, oxygen hole compensation is found. However, Sc 3+, In3+, and Y3+ show the formation of a reduced Ce3+ cation and an uncompensated oxygen hole, similar to La3+. These results suggest that the ionic radius of trivalent dopants strongly influences the final defect formed when doping ceria with 3+ cations. In light of these findings, experimental investigations of these systems will be welcome.

Multimode Atomic Pattern Formation via Enhanced Light-atom Interactions

The nonlinear interaction between light and atoms is an extensive field of study with a broad range of applications in quantum information science and condensed matter physics. Nonlinear optical phenomena occurring in cold atoms are particularly interesting because such slowly moving atoms can spatially organize into density gratings, which allows for studies involving optical interactions with structured materials. In this thesis, I describe a novel nonlinear optical effect that arises when cold atoms spatially bunch in an optical lattice. I show that employing this spatial atomic bunching provides access to a unique physical regime with reduced thresholds for nonlinear optical processes and enhanced material properties. Using this method, I observe the nonlinear optical phenomenon of transverse optical pattern formation at record-low powers. These transverse optical patterns are generated by a wave- mixing process that is mediated by the cold atomic vapor. The optical patterns are highly multimode and induce rich non-equilibrium atomic dynamics. In particular, I find that there exists a synergistic interplay between the generated optical pat- terns and the atoms, wherein the scattered fields help the atoms to self-organize into new, multimode structures that are not externally imposed on the atomic sample. These self-organized structures in turn enhance the power in the optical patterns. I provide the first detailed investigation of the motional dynamics of atoms that have self-organized in a multimode geometry. I also show that the transverse optical patterns induce Sisyphus cooling in all three spatial dimensions, which is the first observation of spontaneous three-dimensional cooling. My experiment represents a unique means by which to study nonlinear optics and non-equilibrium dynamics at ultra-low required powers.

Effects of lycopene on the induction of foam cell formation by modified LDL.

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by ∼30% by lycopene. In addition, lycopene inhibited IL-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1β or TNF-α release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect.

Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses

Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.

Synergistic nisin-polymyxin combinations for the control of Pseudomonas biofilm formation

The emergence and dissemination of multi-drug resistant pathogens is a global concern. Moreover, even greater levels of resistance are conferred on bacteria when in the form of biofilms (i.e., complex, sessile communities of bacteria embedded in an organic polymer matrix). For decades, antimicrobial peptides have been hailed as a potential solution to the paucity of novel antibiotics, either as natural inhibitors that can be used alone or in formulations with synergistically acting antibiotics. Here, we evaluate the potential of the antimicrobial peptide nisin to increase the efficacy of the antibiotics polymyxin and colistin, with a particular focus on their application to prevent biofilm formation of Pseudomonas aeruginosa. The results reveal that the concentrations of polymyxins that are required to effectively inhibit biofilm formation can be dramatically reduced when combined with nisin, thereby enhancing efficacy, and ultimately, restoring sensitivity. Such combination therapy may yield added benefits by virtue of reducing polymyxin toxicity through the administration of significantly lower levels of polymyxin antibiotics.

Lifetime and distribution of ozone and related pollutants in the eastern United States

Most major cities in the eastern United States have air quality deemed unhealthy by the EPA under a set of regulations known as the National Ambient Air Quality Standards (NAAQS). The worst air quality in Maryland is measured in Edgewood, MD, a small community located along the Chesapeake Bay and generally downwind of Baltimore during hot, summertime days. Direct measurements and numerical simulations were used to investigate how meteorology and chemistry conspire to create adverse levels of photochemical smog especially at this coastal location. Ozone (O3) and oxidized reactive nitrogen (NOy), a family of ozone precursors, were measured over the Chesapeake Bay during a ten day experiment in July 2011 to better understand the formation of ozone over the Bay and its impact on coastal communities such as Edgewood. Ozone over the Bay during the afternoon was 10% to 20% higher than the closest upwind ground sites. A combination of complex boundary layer dynamics, deposition rates, and unaccounted marine emissions play an integral role in the regional maximum of ozone over the Bay. The CAMx regional air quality model was assessed and enhanced through comparison with data from NASA’s 2011 DISCOVER-AQ field campaign. Comparisons show a model overestimate of NOy by +86.2% and a model underestimate of formaldehyde (HCHO) by –28.3%. I present a revised model framework that better captures these observations and the response of ozone to reductions of precursor emissions. Incremental controls on electricity generating stations will produce greater benefits for surface ozone while additional controls on mobile sources may yield less benefit because cars emit less pollution than expected. Model results also indicate that as ozone concentrations improve with decreasing anthropogenic emissions, the photochemical lifetime of tropospheric ozone increases. The lifetime of ozone lengthens because the two primary gas-phase sinks for odd oxygen (Ox ≈ NO2 + O3) – attack by hydroperoxyl radicals (HO2) on ozone and formation of nitrate – weaken with decreasing pollutant emissions. This unintended consequence of air quality regulation causes pollutants to persist longer in the atmosphere, and indicates that pollutant transport between states and countries will likely play a greater role in the future.

Ultrasound-assisted electrochemical treatment of wastewaters containing organic pollutants by using novel Ti/Ta2O5-SnO2 electrodes

Advanced oxidation processes (AOPs) are modern methods using reactive hydroxyl radicals for the mineralization of organic pollutants into simple inorganic compounds, such as CO2 and H2O. Among AOPs electrochemical oxidation (EO) is a method suitable for coloured and turbid wastewaters. The degradation of pollutants occurs on electrocatalytic electrodes. The majority of electrodes contain in their structure either expensive materials (diamond and Pt-group metals) or are toxic for the environment compounds (Sb or Pb). One of the main disadvantages of electrochemical method is the polarization and contamination of electrodes due to the deposition of reaction products on their surface, which results in diminishing of the process efficiency. Ultrasound combined with the electrochemical degradation process eliminates electrode contamination because of the continuous mechanical cleaning effect produced by the formation and collapse of acoustic cavitation bubbles near to the electrode surface. Moreover, high frequency ultrasound generates hydroxyl radicals at water sonolysis. Ultrasound-assisted EO is a non-selective method for oxidation of different organic compounds with high degradation efficiencies. The aim of this research was to develop novel sustainable and cost-effective electrodes working as electrocatalysts and test their activity in electrocatalytic oxidation of organic compounds such as dyes and organic acids. Moreover, the goal of the research was to enhance the efficiency of electrocatalytic degradation processes by assisting it with ultrasound in order to eliminate the main drawbacks of a single electrochemical oxidation such as electrodes polarization and passivation. Novel Ti/Ta2O5-SnO2 electrodes were developed and found to be electrocatalytically active towards water (with 5% Ta content, 10 oxide film layers) and organic compounds oxidation (with 7.5% Ta content, 8 oxide film layers) and therefore these electrodes can be applicable in both environmental and energy fields. The synergetic effect of combined electrolysis and sonication was shown while conducting sonoelectrochemical (EO/US) degradation of methylene blue (MB) and formic acid (FA). Complete degradation of MB and FA was achieved after 45 and 120 min of EO/US process respectively in neutral media. Mineralization efficiency of FA over 95% was obtained after 2 h of degradation using high frequency ultrasound (381, 863, 1176 kHz) combined with 9.1 mA/cm2 current density. EO/US degradation of MB provided over 75% mineralization in 8 h. High degradation kinetic rates and mineralization efficiencies of model pollutants obtained in EO/US experiments provide the preconditions for further extrapolation of this treatment method to pilot scale studies with industrial wastewaters.

Mixed Layer formation and restratification in presence of mesoscale and submesoscale turbulence

Recent realistic high resolution modeling studies show a net increase of submesoscale activity in fall and winter when the mixed layer depth is at its maximum. This submesoscale activity increase is associated with a reduced deepening of the mixed layer. Both phenomena can be related to the development of mixed layer instabilities, which convert available potential energy into submesoscale eddy kinetic energy and contribute to a fast restratification by slumping the horizontal density gradient in the mixed layer. In the present work, the mixed layer formation and restratification was studied by uniformly cooling a fully turbulent zonal jet in a periodic channel at different resolutions, from eddy resolving (10 km) to submesoscale permitting (2 km). The effect of the submesoscale activity, highlighted by these different horizontal resolutions, was quantified in terms of mixed layer depth, restratification rate and buoyancy fluxes. Contrary to many idealized studies focusing on the restratification phase only, this study addresses a continuous event of mixed layer formation followed by its complete restratification. The robustness of the present results was established by ensemble simulations. The results show that, at higher resolution, when submesoscale starts to be resolved, the mixed layer formed during the surface cooling is significantly shallower and the total restratification almost three times faster. Such differences between coarse and fine resolution models are consistent with the submesoscale upward buoyancy flux, which balances the convection during the formation phase and accelerates the restratification once the surface cooling is stopped. This submesoscale buoyancy flux is active even below the mixed layer. Our simulations show that mesoscale dynamics also cause restratification, but on longer time scales. Finally, the spatial distribution of the mixed layer depth is highly heterogeneous in the presence of submesoscale activity, prompting the question of whether it is possible to parameterize submesoscale effects and their effects on the marine biology as a function of a spatially-averaged mixed layer depth.

Reduced graphene oxide and Ag wrapped TiO2 photocatalyst for enhanced visible light photocatalysis

A well-organised reduced graphene oxide (RGO) and silver (Ag) wrapped TiO2 nano-hybrid was successfully achieved through a facile and easy route. The inherent characteristics of the synthesized RGO-Ag/TiO2 were revealed through crystalline phase, morphology, chemical composition, Raman scattering, UV-visible absorption, and photoluminescence analyses. The adopted synthesis route significantly controlled the uniform formation of silver nanoparticles and contributed for the absorption of light in the visible spectrum through localized surface plasmon resonance effects. The wrapped RGO nanosheets triggered the electron mobility and promoted visible light shift towards red spectrum. The accomplishment of synergised effect of RGO and Ag well degraded Bisphenol A under visible light irradiation with a removal efficiency of 61.9%.

Sodium hypochlorite effects on dentin bond strength and acid-base resistant zone formation by adhesive systems

Aim: To evaluate the effects of 10% NaOCl gel application on the dentin bond strengths and morphology of resin-dentin interfaces formed by three adhesives. Methods: Two etch-and-rinse adhesives (One-Step Plus, Bisco Inc. and Clearfil Photo Bond, Kuraray Noritake Dental) and one self-etch adhesive (Clearfil SE Bond, Kuraray Noritake Dental) were applied on dentin according to the manufacturers’ instructions or after the treatment with 10% NaOCl (ED-Gel, Kuraray Noritake Dental) for 60 s. For interfacial analysis, specimens were subjected to acid-base challenge and observed by SEM to identify the formation of the acid-base resistant zone (ABRZ). For microtensile bond strength, the same groups were investigated and the restored teeth were thermocycled (5,000 cycles) or not before testing. Bond strength data were subjected to two-way ANOVA and Tukey’s test (p<0.05). Results: NaOCl application affected the bond strengths for One-Step Plus and Clearfil Photo Bond. Thermocycling reduced the bond strengths for Clearfil Photo Bond and Clearfil SE Bond when used after NaOCl application and One-Step Plus when used as recommended by manufacturer. ABRZ was observed adjacent to the hybrid layer for self-etch primer. The etch-and-rinse systems showed external lesions after acid-base challenge and no ABRZ formation when applied according to manufacturer’s instructions. Conclusions: 10% NaOCl changed the morphology of the bonding interfaces and its use with etch-&-rinse adhesives reduced the dentin bond strength. Formation of ABRZ was material-dependent and the interface morphologies were different among the tested materials.

Infralimbic cortex controls the activity of the hypothalamus-pituitary adrenal axis and the formation of aversive memory: effects of environmental enrichment

The aim of the present study was to investigate the effects of the stimulation and inhibition of the ventral part of the medial prefrontal cortex (infralimbic cortex) on basal and stress-induced plasma levels of corticosterone and on the acquisition of aversive memory in animals maintained in control and environmental enrichment (EE) conditions. Intracortical microinjections of the GABAA antagonist picrotoxin and agonist muscimol were performed in male Wistar rats to stimulate and inhibit, respectively, the activity of the infralimbic cortex. Injections were performed 60 min before foot shock stress and training in the inhibitory avoidance task. Picrotoxin injections into the infralimbic cortex increased basal plasma levels of corticosterone. These increases were higher in EE rats which suggest that EE enhances the control exerted by infralimbic cortex over the hypothalamus-pituitary-adrenal (HPA) axis and corticosterone release. Muscimol injections into the infralimbic cortex reduced the stress-induced plasma levels of corticosterone and the retention latency 24 h after training in the inhibitory avoidance performance in control and EE animals, respectively. These results further suggest that the infralimbic cortex is required for the activation of the HPA axis during stress and for the acquisition of contextual aversive memories.