Effects of Anesthetic Ketamine on Anxiety-Like Behaviour in Rats

There is scarce information regarding the effects of anesthetic doses of the non-competitive N-methyl-d-aspartate receptor antagonist ketamine on anxiety. The current study evaluated the acute effects of intraperitoneally (i.p.) administered anesthetic ketamine (100 mg/kg) i.p. on anxiety in rats. For this purpose, the light/dark and the open field tests were utilized. The effects of anesthetic ketamine on motility were also examined using a motility cage. In the light/dark test, anesthetic ketamine, administered 24 h before testing reduced the number of transitions between the light and dark compartments and the time spent in the light compartment in the rats compared with their control cohorts. In addition, ketamine was found to exert a depressive effect on rats’ motility. In the open field test, animals treated with anesthetic ketamine 24 h before testing spent essentially no time in the central area of the apparatus, decreased horizontal ambulatory activity, and preserved to a certain extent their exploratory behaviour compared to their control counterparts. The results suggest that, in spite of its hypokinetic effect, a single anesthetic ketamine administration apparently induces an anxiety-like state, while largely preserving exploratory behaviour in the rat. These effects were time-dependent they since they were extinguished when testing was carried out 48 h after anesthetic ketamine administration.

     

Plant volatiles induced by herbivore egg deposition affect insects of different trophic levels

Plants release volatiles induced by herbivore feeding that may affect the diversity and composition of plant-associated arthropod communities. However, the specificity and role of plant volatiles induced during the early phase of attack, i.e. egg deposition by herbivorous insects, and their consequences on insects of different trophic levels remain poorly explored. In olfactometer and wind tunnel set-ups, we investigated behavioural responses of a specialist cabbage butterfly (Pieris brassicae) and two of its parasitic wasps (Trichogramma brassicae and Cotesia glomerata) to volatiles of a wild crucifer (Brassica nigra) induced by oviposition of the specialist butterfly and an additional generalist moth (Mamestra brassicae). Gravid butterflies were repelled by volatiles from plants induced by cabbage white butterfly eggs, probably as a means of avoiding competition, whereas both parasitic wasp species were attracted. In contrast, volatiles from plants induced by eggs of the generalist moth did neither repel nor attract any of the tested community members. Analysis of the plant's volatile metabolomic profile by gas chromatography-mass spectrometry and the structure of the plant-egg interface by scanning electron microscopy confirmed that the plant responds differently to egg deposition by the two lepidopteran species. Our findings imply that prior to actual feeding damage, egg deposition can induce specific plant responses that significantly influence various members of higher trophic levels.     

11β-HSD1 Inhibition by RL-118 Promotes Autophagy and Correlates with Reduced Oxidative Stress and Inflammation,Enhancing Cognitive Performance in SAMP8 Mouse Model

Elevated glucocorticoid (GC) exposure is widely accepted as a key factor in the age-related cognitive decline in rodents and humans. 11β-HSD1 is a key enzyme in the GCs pathway, catalyzing the conversion of 11β-dehydrocorticosterone to corticosterone in mice, with possible implications in neurodegenerative processes and cognitive impairment. Here, we determined the effect of a new 11β-HSD1 inhibitor, RL-118, administered to 12-month-old senescence-accelerated mouse-prone 8 (SAMP8) mice with neuropathological AD-like hallmarks and widely used as a rodent model of cognitive dysfunction. Behavioral tests (open field and object location) and neurodegeneration molecular markers were studied. After RL-118 treatment, increased locomotor activity and cognitive performance were found. Likewise, we found changes in hippocampal autophagy markers such as Beclin1, LC3B, AMPKα, and mTOR, indicating a progression in the autophagy process. In line with autophagy increase, a diminution in phosphorylated tau species (Ser 396 and Ser 404) jointly with an increase in ADAM10 and sAPPα indicated that an improvement in removing the abnormal proteins by autophagy might be implicated in the neuroprotective role of the 11β-HSD1 inhibitor. In addition, gene expression of oxidative stress (OS) and inflammatory markers, such as Hmox1, Aldh2, Il-1β, and Ccl3, were reduced in old treated mice in comparison to that of the control group. Consistent with this, we further demonstrate a significant correlation with autophagy markers and cognitive improvement and significant inverse correlation with autophagy, OS, and neuroinflammation markers. We concluded that inhibition of 11β-HSD1 by RL-118 prevented neurodegenerative processes and cognitive decline, acting on autophagy process, being an additional neuroprotective mechanism not described previously.     

Children with well controlled epilepsy possess different spatio-temporal patterns of causal network connectivity during a visual working memory task

Using spectral Granger causality (GC) we identified distinct spatio-temporal causal connectivity (CC) patterns in groups of control and epileptic children during the execution of a one-back matching visual discrimination working memory task. Differences between control and epileptic groups were determined for both GO and NOGO conditions. The analysis was performed on a set of 19-channel EEG cortical activity signals. We show that for the GO task, the highest brain activity in terms of the density of the CC networks is observed in α band for the control group while for the epileptic group the CC network seems disrupted as reflected by the small number of connections. For the NOGO task, the denser CC network was observed in θ band for the control group while widespread differences between the control and the epileptic group were located bilaterally at the left temporal-midline and parietal areas. In order to test the discriminative power of our analysis, we performed a pattern analysis approach based on fuzzy classification techniques. The performance of the classification scheme was evaluated using permutation tests. The analysis demonstrated that, on average, 87.6 % of the subjects were correctly classified in control and epileptic. Thus, our findings may provide a helpful insight on the mechanisms pertaining to the cognitive response of children with well controlled epilepsy and could potentially serve as “functional” biomarkers for early diagnosis.     

Somatostatin receptors (sst2) regulate cGMP production in rat retina

The present study investigated the effect of somatostatin in the regulation of cGMP levels in rat retina and the mechanisms involved in this process. Isolated rat retinas were treated alone or in the presence of somatostatin (0.01-10 microM), BIM23014 (sst2 agonist, 0.01-10 microM), L-796,778 (sst3 agonist, 10 microM), somatostatin (0.1 microM) in combination with CYN154806 (sst2 antagonist, 1 microM), N(G)-methyl-L-arginine acetate salt (NMMA, inhibitor of the nitric oxide synthase (NOS), 250 microM), orthovanadate (inhibitor of tyrosine phosphatase, SHP-1, 1 microM), and arginine alone (250 microM). cGMP levels were quantified by ELISA. Immunohistochemistry studies were performed for the detection of cGMP and nNOS, while Western blot analysis was employed for the detection of SHP-1. Somatostatin increased cGMP levels in a concentration-dependent manner. This increase was inhibited by CYN154806. BIM23014 increased cGMP levels only at the concentration of 10 microM, while L-796,778 had no effect. NMMA blocked completely the somatostatin stimulated increase of cGMP levels and nNOS was detected in rat retina. cGMP immunoreactivity was observed primarily in bipolar cells only of nitroprusside-treated retinas. SHP-1 inhibition by orthovanadate reduced the somatostatin effect in a statistically significant manner. These results suggest that a SRIF/SHP-1/NO/cGMP mechanism underlies the actions of somatostatin in the retina and in its influence of retinal circuitry.     

Silver‐spoon upbringing improves early‐life fitness but promotes reproductive ageing in a wild bird

Early‐life conditions can have long‐lasting effects and organisms that experience a poor start in life are often expected to age at a faster rate. Alternatively, individuals raised in high‐quality environments can overinvest in early‐reproduction resulting in rapid ageing. Here we use a long‐term experimental manipulation of early‐life conditions in a natural population of collared flycatchers (Ficedula albicollis), to show that females raised in a low‐competition environment (artificially reduced broods) have higher early‐life reproduction but lower late‐life reproduction than females raised in high‐competition environment (artificially increased broods). Reproductive success of high‐competition females peaked in late‐life, when low‐competition females were already in steep reproductive decline and suffered from a higher mortality rate. Our results demonstrate that ‘silver‐spoon’ natal conditions increase female early‐life performance at the cost of faster reproductive ageing and increased late‐life mortality. These findings demonstrate experimentally that natal environment shapes individual variation in reproductive and actuarial ageing in nature.     

Replication and Predictive Value of SNPs Associated with Melanoma and Pigmentation Traits in a Southern European Case-Control Study

Background

Genetic association studies have revealed numerous polymorphisms conferring susceptibility to melanoma. We aimed to replicate previously discovered melanoma-associated single-nucleotide polymorphisms (SNPs) in a Greek case-control population, and examine their predictive value.

Methods

Based on a field synopsis of genetic variants of melanoma (MelGene), we genotyped 284 patients and 284 controls at 34 melanoma-associated SNPs of which 19 derived from GWAS. We tested each one of the 33 SNPs passing quality control for association with melanoma both with and without accounting for the presence of well-established phenotypic risk factors. We compared the risk allele frequencies between the Greek population and the HapMap CEU sample. Finally, we evaluated the predictive ability of the replicated SNPs.

Results

Risk allele frequencies were significantly lower compared to the HapMap CEU for eight SNPs (rs16891982 – SLC45A2, rs12203592 – IRF4, rs258322 – CDK10, rs1805007 – MC1R, rs1805008 - MC1R, rs910873 - PIGU, rs17305573- PIGU, and rs1885120 - MTAP) and higher for one SNP (rs6001027 – PLA2G6) indicating a different profile of genetic susceptibility in the studied population. Previously identified effect estimates modestly correlated with those found in our population (r = 0.72, P<0.0001). The strongest associations were observed for rs401681-T in CLPTM1L (odds ratio [OR] 1.60, 95% CI 1.22–2.10; P = 0.001), rs16891982-C in SCL45A2 (OR 0.51, 95% CI 0.34–0.76; P = 0.001), and rs1805007-T in MC1R (OR 4.38, 95% CI 2.03–9.43; P = 2×10⁻⁵). Nominally statistically significant associations were seen also for another 5 variants (rs258322-T in CDK10, rs1805005-T in MC1R, rs1885120-C in MYH7B, rs2218220-T in MTAP and rs4911442-G in the ASIP region). The addition of all SNPs with nominal significance to a clinical non-genetic model did not substantially improve melanoma risk prediction (AUC for clinical model 83.3% versus 83.9%, p = 0.66).

Conclusion

Overall, our study has validated genetic variants that are likely to contribute to melanoma susceptibility in the Greek population.     

Testing the species--genetic diversity correlation in the Aegean archipelago: toward a haplotype-based macroecology?

A positive correlation between species diversity and genetic diversity has been proposed, consistent with neutral predictions in macroecology. We assessed the species--genetic diversity correlation in tenebrionid beetle communities of the Aegean archipelago on 15 islands of different sizes, distances to mainland, and ages of isolation. Alpha and beta diversity of species and haplotypes were assessed using sequences of > 1,000 individuals (mitochondrial cytochrome oxidase 1 and nuclear muscular protein 20). We show that (i) there is a strong species-area and haplotype-area relationship; (ii) species richness in island communities is correlated with intraspecific genetic diversity in the constituent species except when island size or distance to mainland is factored out in partial correlations; (iii) community similarity declines exponentially at an increasing rate when calculated on the basis of species, nuclear, and mtDNA haplotypes; and (iv) distance decay of community similarity is slower in dispersive sand-dwelling lineages compared with less dispersive lineages that are not sand obligate. Taken together, these correlated patterns at the species and haplotype level are consistent with individual-based stochastic dispersal proposed by neutral theories of biodiversity. The results also demonstrate the utility of haplotype data for exploring macroecological patterns in poorly known biota and predicting large-scale biodiversity patterns based on genetic inventories of local samples.     

Short-Term Exposure to Nickel Alters the Adult Rat Brain Antioxidant Status and the Activities of Crucial Membrane-Bound Enzymes: Neuroprotection by L-Cysteine

Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl₂, 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na⁺,K⁺-ATPase, and Mg²⁺-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above-mentioned parameters were measured spectrophotometrically. Rats treated with Ni exhibited a significant reduction in brain TAS (-47%, p < 0.001, BvsA) that was efficiently limited by the co-administration of Cys (-4%, p > 0.05, DvsA; +83%, p < 0.001, DvsB), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Ni (+30%, p < 0.001, BvsA) and Cys (+62%, p < 0.001, CvsA), while it tended to adjust to control levels by the co-administration of Ni and Cys (+13%, p < 0.001, DvsA; −13%, p < 0.001, DvsB). The activity of rat brain Na⁺,K⁺-ATPase was significantly decreased by Ni-administration (−49%, p < 0.001, BvsA), while Cys supplementation could not reverse this decrease (-44%, p < 0.001, DvsA). The activity of Mg²⁺-ATPase was not affected by Ni-administration (−3%, p > 0.05, BvsA), but was significantly reduced when combined with Cys administration (−17%, p < 0.001, DvsA). The above findings suggest that Ni short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed to control levels by Cys co-administration; Cys could thus be considered (for future applications) as a potential neuroprotective agent against chronic exposure to Ni. The activity of Na⁺,K⁺-ATPase that was inhibited by Ni, could not be reversed by Cys co-administration. The matter requires further investigation in order to fully elucidate the spectrum of the neurotoxic effects of Ni.