The fingerprint of the 2018 drought in Europe on ground-based atmospheric CO2 measurements.

During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.

Ion-ion dynamic structure factor, acoustic modes, and equation of state of two-temperature warm dense aluminum.

The ion-ion dynamical structure factor and the equation of state of warm dense aluminum in a two-temperature quasiequilibrium state, with the electron temperature higher than the ion temperature, are investigated using molecular-dynamics simulations based on ion-ion pair potentials constructed from a neutral pseudoatom model. Such pair potentials based on density functional theory are parameter-free and depend directly on the electron temperature and indirectly on the ion temperature, enabling efficient computation of two-temperature properties. Comparison with ab initio simulations and with other average-atom calculations for equilibrium aluminum shows good agreement, justifying a study of quasiequilibrium situations. Analyzing the van Hove function, we find that ion-ion correlations vanish in a time significantly smaller than the electron-ion relaxation time so that dynamical properties have a physical meaning for the quasiequilibrium state. A significant increase in the speed of sound is predicted from the modification of the dispersion relation of the ion acoustic mode as the electron temperature is increased. The two-temperature equation of state including the free energy, internal energy, and pressure is also presented.

Effects of halogens on European air-quality.

Halogens (Cl, Br) have a profound influence on stratospheric ozone (O3). They (Cl, Br and I) have recently also been shown to impact the troposphere, notably by reducing the mixing ratios of O3 and OH. Their potential for impacting regional air-quality is less well understood. We explore the impact of halogens on regional pollutants (focussing on O3) with the European grid of the GEOS-Chem model (0.25° × 0.3125°). It has recently been updated to include a representation of halogen chemistry. We focus on the summer of 2015 during the ICOZA campaign at the Weybourne Atmospheric Observatory on the North Sea coast of the UK. Comparisons between these observations together with those from the UK air-quality network show that the model has some skill in representing the mixing ratios/concentration of pollutants during this period. Although the model has some success in simulating the Weybourne ClNO2 observations, it significantly underestimates ClNO2 observations reported at inland locations. It also underestimates mixing ratios of IO, OIO, I2 and BrO, but this may reflect the coastal nature of these observations. Model simulations, with and without halogens, highlight the processes by which halogens can impact O3. Throughout the domain O3 mixing ratios are reduced by halogens. In northern Europe this is due to a change in the background O3 advected into the region, whereas in southern Europe this is due to local chemistry driven by Mediterranean emissions. The proportion of hourly O3 above 50 nmol mol-1 in Europe is reduced from 46% to 18% by halogens. ClNO2 from N2O5 uptake onto sea-salt leads to increases in O3 mixing ratio, but these are smaller than the decreases caused by the bromine and iodine. 12% of ethane and 16% of acetone within the boundary layer is oxidised by Cl. Aerosol response to halogens is complex with small (∼10%) reductions in PM2.5 in most locations. A lack of observational constraints coupled to large uncertainties in emissions and chemical processing of halogens make these conclusions tentative at best. However, the results here point to the potential for halogen chemistry to influence air quality policy in Europe and other parts of the world.

Microinfarcts in an older population-representative brain donor cohort (MRC CFAS): Prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel Disease.

INTRODUCTION: Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship with dementia, mobility and cerebrovascular disease in an older population-representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD). METHODS: Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n = 331). Nine brain areas were staged according to the number of areas affected. RESULTS: 36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95% CI 1.02; 1.96, P = 0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95% CI 1.05-1.74; P 0.018) and falls (OR 1.96, 95% CI 1.11-3.43; P = 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions (WMLs), lacunes and significant arteriosclerosis, were assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of WMLs, lacunes and microinfarcts. CONCLUSION: Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on WMLs, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis.

Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat.

BACKGROUND AND PURPOSE: Ceftriaxone is a ß-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. × 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α-synuclein, Akt and GSK3ß were analysed in the nucleus accumbens. KEY RESULTS: Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3ß signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. CONCLUSIONS AND IMPLICATIONS: These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens.

Serotonin in the ventral hippocampus modulates anxiety-like behavior during amphetamine withdrawal.

Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reducing 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the ventral hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-dihydroxytryptamine (5,7-DHT) into the ventral hippocampus, which produced a 83% decrease in ventral hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing ventral hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting that diminished ventral hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the ventral hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5-mg/kg, i.p.) or saline for 2weeks, and at 2weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5µM) bilaterally into the ventral hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by ventral hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the ventral hippocampus are critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse.

Thermal expansion of free-standing graphene: benchmarking semi-empirical potentials.

The thermodynamical properties of free-standing graphene have been investigated under constant zero pressure as a function of temperature using Monte Carlo simulations. A variety of atomistic models have been used, including the simple three-body Stillinger potential and a series of bond-order many-body potentials based on the Tersoff-Brenner seminal models, with recent reparametrizations dedicated to graphene, extensions to medium-range or long-range dispersion corrections. In addition, we have also tested a tight-binding potential in the fourth-moment approximation. The simulations reveal significant discrepancies in the in-plane lattice parameter and the thermal expansion coefficient, which despite showing monotonically increasing variations with temperature, can be positive, negative or change sign at moderate temperature depending on the potential. Comparison with existing experimental and theoretical data obtained from complementary approaches indicates that empirical potentials limited to nearest-neighbour interactions give rather dispersed results, and that van der Waals corrections generally tend to flatten the variations of the in-plane lattice constant, in contradiction with experiment. Only the medium-range corrected potentials of Los and Fasolino, as well as the tight-binding model in the fourth-moment approximation, are reasonably close to the reference results near room temperature. Our results suggest that classical potentials should be used with caution for thermal properties.

Novel method for sludge blanket measurements.

The most widely used methods for sludge blanket measurements are based on acoustic or optic principles. In operation, both methods are expensive and often maintenance-intensive. Therefore a novel, reliable and simple method for sludge blanket measurement is proposed. It is based on the differential pressure measurement in the sludge zone compared with the differential pressure in the clear water zone, so that it is possible to measure the upper and the lower sludge level in a tank. Full-scale tests of this method were done in the secondary clarifier at the waste water treatment plant in Hecklingen, Germany. The result shows a good approximation of the manually measured sludge level.

Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds.

INTRODUCTION: Magnetic resonance imaging (MRI) cerebral microbleeds (CMB) arise from ferromagnetic haemosiderin iron assumed to derive from extravasation of erythrocytes. Light microscopy of ageing brain frequently reveals foci of haemosiderin from single crystalloids to larger, predominantly perivascular, aggregates. The pathological and radiological relationship between these findings is not resolved. METHODS: Haemosiderin deposition and vascular pathology in the putamen were quantified in 200 brains donated to the population-representative Medical Research Council Cognitive Function and Ageing Study. Molecular markers of gliosis and tissue integrity were assessed by immunohistochemistry in brains with highest (n = 20) and lowest (n = 20) levels of putamen haemosiderin. The association between haemosiderin counts and degenerative and vascular brain pathology, clinical data, and the haemochromatosis (HFE) gene H63D genotype were analysed. The frequency of MRI CMB in 10 cases with highest and lowest burden of putamen haemosiderin, was compared using post mortem 3T MRI. RESULTS: Greater putamen haemosiderin was significantly associated with putaminal indices of small vessel ischaemia (microinfarcts, P < 0.05; arteriolosclerosis, P < 0.05; perivascular attenuation, P < 0.001) and with lacunes in any brain region (P < 0.023) but not large vessel disease, or whole brain measures of neurodegenerative pathology. Higher levels of putamen haemosiderin correlated with more CMB (P < 0.003). CONCLUSIONS: The MRI-CMB concept should take account of brain iron homeostasis, and small vessel ischaemic change in later life, rather than only as a marker for minor episodes of cerebrovascular extravasation. These data are of clinical relevance, suggesting that basal ganglia MRI microbleeds may be a surrogate for ischaemic small vessel disease rather than exclusively a haemorrhagic diathesis.

Periodontal conditions in vegetarians: a clinical study.

BACKGROUND/OBJECTIVES: Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. SUBJECTS/METHODS: A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: P<0.05). RESULTS: Well known periodontal risk factors like age, gender and smoking habits were equally distributed within each group (71 females, 29 males, respectively and 10 smokers in each group; mean age: 41.45 years vegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (P<0.001) and less mobile teeth (P=0.013). Dental examinations revealed significantly less missing teeth (P=0.018) but also more decayed (P=0.001) and eroded (P=0.026) teeth in vegetarians. Furthermore, vegetarians had a higher level of education (P<0.001), but visited dentists significantly less frequent. CONCLUSIONS: Vegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.

Calcium dysregulation in relation to Alzheimer-type pathology in the ageing brain.

AIMS: Calcium dyshomeostasis is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease. However, much of the previous research has focused on changes in neuronal calcium signalling. In a recent microarray study we identified dysregulation of several key signalling pathways including the Ca(2+) signalling pathway in astrocytes as Alzheimer-type pathology developed. In this study we sought to determine the expression of calpain-10 and calcium/calmodulin-dependent kinase alpha (CamKIIα) in relation to Alzheimer-type pathology in a population-based study. METHODS: Using post mortem temporal cortex samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) ageing brain cohort we examined calpain-10 and CamKIIα gene and protein expression using quantitative polymerase chain reaction and immunohistochemistry. RESULTS: We demonstrate that astrocytic expression of calpain-10 is up-regulated, and CamKIIα down-regulated with increasing Braak stage. Using immunohistochemistry we confirm protein expression of calpain-10 in astrocytes throughout the temporal cortex and demonstrate that calpain-10 immunoreactivity is correlated with both local and global measures of Alzheimer-type pathology. In addition, we identify a subpopulation of calpain-10 immunoreactive interlaminar astrocytes that extend processes deep into the cortex. CamKIIα is predominantly neuronal in localization and is associated with the presence of diffuse plaques in the ageing brain. DISCUSSION: Dysregulated expression of key calcium signalling molecules occurs with progression of Alzheimer-type pathology in the ageing brain, highlighting the need for further functional studies of astrocytic calcium signalling with respect to disease progression.

Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice.

Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders.

[Reinnervation and neurostimulation of the larynx]. / Reinnervation und Neurostimulation des Kehlkopfs.

Dynamic rehabilitation of vocal fold paralysis (VFP) should receive more emphasis in the future. In unilateral immobility with signs of atrophy and wide glottal gap, non-selective reinnervation with ansa cervicalis may become an alternative to augmentation and thyroplasty. For bilateral VFP progress has been made in the concepts of selective reinnervation and neurostimulation (pacing). These new therapies have the potential to restore near normal respiration-without compromising the voice quality-and may contribute to the development of larynx transplantation surgery.

[Staging with 18F-FDG-PET/CT influences stage-specific survival in advanced non-small cell lung cancer (NSCLC)]. / Der Einfluss des F-18-FDG-PET/CT auf das stadienbezogene Gesamtüberleben beim fortgeschrittenen nicht-kleinzelligen Lungenkarzinom (NSCLC).

BACKGROUND: PET/CT investigation with 18F-fluorodeoxyglucose (FDG) has a high sensitivity (89 - 100 %) and good specificity (79 - 95 %) for the diagnosis of NSCLC. Currently, it is mainly used in preoperative staging. This leads in approximately 15 % of these cases to the diagnosis of metastatic disease that was neither clinically suspected nor seen in previously performed conventional imaging. We hypothesised that including these cases in the palliative stage IV group would have an influence on overall survival. AIM: The aim of this study was to compare the overall survival (OS) of patients with stage IV NSCLC who underwent FDG-PET/CT staging with patients in whom conventional imaging procedures were performed. METHODS: We analysed the OS of all stage IV NSCLC patients diagnosed in our clinic in 2009 (n = 254), 96/254 (38 %) patients were staged with PET/CT and 158/254 (62 %) with conventional imaging (CT group). Survival data were compared by Kaplan-Meier statistics. RESULTS: Patients in the PET/CT group were younger (65 ± 11) than in the CT group (68 ± 10 years; p = 0.008). The median OS of all patients was 246 (range: 217 - 275) days; 338 (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) days in the CT group (p = 0.001), stating a difference of 131 days (4.4 months) in median OS. CONCLUSION: The use of FDG-PET/CT staging mainly in the preoperative setting leads to stage migration of patients with a better prognosis into the worst stage (IV) and thus longer survival within this subgroup. This survival benefit is unrelated to treatment and needs to be addressed in future studies.

Effects of cooked navy bean powder on apparent total tract nutrient digestibility and safety in healthy adult dogs.

Dry beans (Phaseolus vulgaris L., Fabaceae) are a low glycemic index food containing protein, fiber, minerals, essential vitamins, and bioactive compounds and have not been evaluated for inclusion in commercial canine diets. The objective of this study was to establish the apparent total tract digestibility and safety of cooked navy bean powder when incorporated into a canine diet formulation at 25% (wt/wt) compared with a macro- and micro-nutrient matched control. Twenty-one healthy, free-living, male and female adult dogs of different breeds were used in a randomized, blinded, placebo controlled, 28-d dietary intervention study. Apparent total tract energy and nutrient digestibility of the navy bean powder diet were compared with the control diet. Digestibilities and ME content were 68.58 and 68.89% DM, 78.22 and 79.49% CP, 77.57 and 74.91% OM, 94.49 and 93.85% acid hydrolyzed fat, and 3,313 and 3,195 kcal ME/kg for the navy bean diet and control diet, respectively. No differences were observed between the groups. No increased flatulence or major change in fecal consistency was observed. Navy bean powder at 25% (wt/wt) of total diet was determined to be palatable (on the basis of intake and observation) and digestible in a variety of dog breeds. No changes were detected in clinical laboratory values, including complete blood counts, blood biochemical profiles, and urinalysis in either the bean or control diet groups. These results indicate that cooked navy bean powder can be safely included as a major food ingredient in canine diet formulations and provide a novel quality protein source, and its use warrants further investigation as a functional food for chronic disease control and prevention.

Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression.

Components of the brain's dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35-P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc), and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence.

Serotonergic neurotransmission in the ventral hippocampus is enhanced by corticosterone and altered by chronic amphetamine treatment.

The ventral hippocampus modulates anxiety-like behavior in rats, and serotonergic transmission within the hippocampus facilitates adaptation to stress. Chronic amphetamine treatment results in anxiety-like behavior in rats and reduced monoamine concentrations in the ventral hippocampus. Since reduced hippocampal serotonergic transmission in response to stress is observed in rats that display high anxiety-like behavior, anxiety states in amphetamine-treated rats may be associated with reduced stress-related serotonergic transmission in the hippocampus. Therefore, using in vivo microdialysis in anesthetized rats, we investigated the effect of corticosterone infused locally into the ventral hippocampus on serotonergic transmission, and the effect of chronic amphetamine pretreatment on corticosteroid receptor protein expression and the corticosterone-induced serotonergic response. Extracellular serotonin in the ventral hippocampus was increased by corticosterone in drug naive rats, and this corticosterone-induced serotonin augmentation was blocked by the glucocorticoid receptor antagonist mifepristone. Furthermore, chronic pretreatment with amphetamine abolished the serotonin response to physiologically relevant corticosterone levels and reduced glucocorticoid receptor protein expression. Together, our results suggest that chronic amphetamine exposure reduces serotonergic neurotransmission, in part via alterations to glucocorticoid receptor-facilitation of serotonin release in the rat ventral hippocampus. Reduced serotonergic activity in the ventral hippocampus may contribute to altered stress responses and adaptive coping following repeated drug exposure.

Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer-type pathology in the ageing brain.

AIMS: Increasing evidence suggests a role for oxidative damage to DNA in brain ageing and in neurodegenerative disorders, including Alzheimer's disease. Most studies have focussed on the reduced capacity for DNA repair by neurones, and have not taken into account the effect of oxidative stress on astrocytes, and their contribution to pathology. METHODS: We examined levels of oxidative stress, DNA damage and DNA repair mechanisms in astrocytes in a population-based sample derived from the Medical Research Council Cognitive Function and Ageing Neuropathology Study. RESULTS: We demonstrate wide variation in parameters for oxidative stress and DNA damage in astrocytes in the ageing population. We show that there is a significant reduction (P = 0.002) in the lipid peroxidation marker malondialdehyde with increasing Braak stage in Alzheimer's disease. Furthermore, we demonstrate that expression of the DNA damage-associated molecules H2AX and DNA-dependent protein kinase do not increase with increasing Braak stage, rather there is evidence of a nonsignificant reduction in DNA-dependent protein kinase expression by neurones and astrocytes, and in H2AX by neurones with increasing levels of Alzheimer's type pathology. CONCLUSIONS: These findings suggest that the changes in oxidative stress and the astrocyte DNA damage response are not accounted for as an accumulating effect due to established Alzheimer-type pathology. We hypothesize that astrocyte damage, leading to impaired function, may contribute to the development of ageing brain pathology in some individuals.

Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain.

Astrocyte pathology occurs in association with Alzheimer's disease (AD) and in brain ageing, but is poorly characterised. We sought to define the detailed cellular pathology of astrocytes, the extent of population variation and the relationship to Alzheimer-type changes in a population-based cohort. Three staining patterns were associated with GFAP and excitatory amino acid transporter 2 (EAAT2): minimal, moderate or extensive immunoreactivity. GFAP and EAAT2 expression were inversely related (p=0.015), with trends to increased expression of GFAP (p=0.019) and decreased expression of EAAT2 (p=ns) with increasing Braak stage. GFAP and EAAT2 correlated incompletely with beta-amyloid and tau immunoreactivity. However, gliosis increased with increasing burden of neuritic (p=0.011), but not diffuse (p=ns), plaques. Double-staining revealed distinct subsets of astrocytes; GFAP(+)EAAT(-), GFAP(-)EAAT(+), or GFAP(+)EAAT(+). In contrast to the variation in GFAP and EAAT2, levels of EAAT1 and S100B showed consistent staining patterns. Alzheimer-type pathology only partially explains the variation in gliosis and astrocyte functional markers, suggesting that other factors contribute to the population variance in astrocyte pathology.