The effect of modafinil on the rat dopamine transporter and dopamine receptors D1–D3 paralleling cognitive enhancement in the radial arm maze

A series of drugs have been reported to increase memory performance modulating the dopaminergic system and herein modafinil was tested for its working memory (WM) enhancing properties. Reuptake inhibition of dopamine, serotonin (SERT) and norepinephrine (NET) by modafinil was tested. Sixty male Sprague–Dawley rats were divided into six groups (modafinil-treated 1–5–10 mg/kg body weight, trained and untrained and vehicle treated trained and untrained rats; daily injected intraperitoneally for a period of 10 days) and tested in a radial arm maze (RAM), a paradigm for testing spatial WM. Hippocampi were taken 6 h following the last day of training and complexes containing the unphosphorylated or phosphorylated dopamine transporter (DAT-CC and pDAT-CC) and complexes containing the D1–3 dopamine receptor subunits (D1–D3-CC) were determined. Modafinil was binding to the DAT but insignificantly to SERT or NET and dopamine reuptake was blocked specifically (IC50 = 11.11 μM; SERT 1547 μM; NET 182 μM). From day 8 (day 9 for 1 mg/kg body weight) modafinil was decreasing WM errors (WMEs) in the RAM significantly and remarkably at all doses tested as compared to the vehicle controls. WMEs were linked to the D2R-CC and the pDAT-CC. pDAT and D1–D3-CC levels were modulated significantly and modafinil was shown to enhance spatial WM in the rat in a well-documented paradigm at all the three doses and dopamine reuptake inhibition with subsequent modulation of D1–3-CC is proposed as a possible mechanism of action. © 2015 Karabacak, Sase, Aher, Sase, Saroja, Cicvaric, Höger, Berger, Bakulev, Sitte, Leban, Monje and Lubec

Egg retention and dispersal activity in the parasitoid wasp, Trichogramma principium

Effects of egg retention on movement and dispersal activity of Trichogramma principium (Hymenoptera, Trichogrammatidae) females were investigated under laboratory conditions. Individual females were observed during one minute in the absence of hosts. Movement activity and dispersal rate were estimated by the length of the track and by the distance from the start point, respectively. Before the test, all wasps during 2 – 4 days were presented with a possibility to parasitize a factitious laboratory host, Sitotroga cerealella Oliv. (Lepidoptera, Gelechiidae). Wasps that had parasitized before the test show significant reduction of spontaneous walking activity and dispersal rate when compared with females that refused to parasitize the non-preferred host (i.e. manifested egg retention). This effect cannot be considered as a direct arrestment reaction to the host because during the test period, no hosts were provided. Thus, egg retention results not only in temporal spread, but also in more intensive spatial dispersal of a group of simultaneously emerged females

Ribonucleotide reductases of Salmonella Typhimurium : transcriptional regulation and differential role in pathogenesis

Ribonucleotide reductases (RNRs) are essential enzymes that carry out the de novo synthesis of deoxyribonucleotides by reducing ribonucleotides. There are three different classes of RNRs (I, II and III), all having different oxygen dependency and biochemical characteristics. Salmonella enterica serovar Typhimurium (S. Typhimurium) harbors class Ia, class Ib and class III RNRs in its genome. We have studied the transcriptional regulation of these three RNR classes in S. Typhimurium as well as their differential function during infection of macrophage and epithelial cells. Deletion of both NrdR and Fur, two main transcriptional regulators, indicates that Fur specifically represses the class Ib enzyme and that NrdR acts as a global repressor of all three classes. A Fur recognition sequence within the nrdHIEF promoter has also been described and confirmed by electrophoretic mobility shift assays (EMSA). In order to elucidate the role of each RNR class during infection, S. Typhimurium single and double RNR mutants (as well as Fur and NrdR mutants) were used in infection assays with macrophage and epithelial cell lines. Our results indicate class Ia to be mainly responsible for deoxyribonucleotide production during invasion and proliferation inside macrophages and epithelial cells. Neither class Ib nor class III seem to be essential for growth under these conditions. However, class Ib is able to maintain certain growth in an nrdAB mutant during the first hours of macrophage infection. Our results suggest that, during the early stages of macrophage infection, class Ib may contribute to deoxyribonucleotide synthesis by means of both an NrdR and a Fur-dependent derepression of nrdHIEF due to hydrogen peroxide production and DNA damage associated with the oxidative burst, thus helping to overcome the host defenses

Abrogated Inflammatory Response Promotes Neurogenesis in a Murine Model of Japanese Encephalitis

Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors

The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries

Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury

Moving carbon between spheres, the potential oxalate-carbonate pathway of Brosimum alicastrum Sw.; Moraceae.

Aims The Oxalate-Carbonate Pathway (OCP) is a biogeochemical process that transfers atmospheric CO2 into the geologic reservoir as CaCO3; however, until now all investigations on this process have focused on species with limited food benefits. This study evaluates a potential OCP associated with Brosimum alicastrum, a Neotropical species with agroforestry potential (ca. 70–200 kg-nuts yr−1), in the calcareous soils of Haiti and Mexico. Methods / results Enzymatic analysis demonstrated significant concentrations of calcium oxalate (5.97 % D.W.) were associated with B. alicastrum tissue in all sample sites. The presence of oxalotrophism was also confirmed with microbiological analyses in both countries. High concentrations of total calcium (>7 g kg−1) and lithogenic carbonate obscured the localised alkalinisation and identification of secondary carbonate associated with the OCP at most sample sites, except Ma Rouge, Haiti. Soils adjacent to subjects in Ma Rouge demonstrated an increase in pH (0.63) and CaCO3 concentration (5.9 %) that, when coupled with root-like secondary carbonate deposits in Mexico, implies that the OCP does also occur in calcareous soils. Conclusions Therefore this study confirms that the OCP also occurs in calcareous soils, adjacent to B. alicastrum, and could play a fundamental and un-accounted role in the global calcium-carbon coupled cycle

Herschel/HIFI measurements of the ortho/para ratio in water towards Sagittarius B2(M) and W31C*

We present Herschel/HIFI observations of the fundamental rotational transitions of ortho- and para-H216O and H218O in absorption towards Sagittarius B2(M) and W31C. The ortho/para ratio in water in the foreground clouds on the line of sight towards these bright continuum sources is generally consistent with the statistical high-temperature ratio of 3, within the observational uncertainties. However, somewhat unexpectedly, we derive a low ortho/para ratio of 2.35 ± 0.35, corresponding to a spin temperature of ~27 K, towards Sagittarius B2(M) at velocities of the expanding molecular ring. Water molecules in this region appear to have formed with, or relaxed to, an ortho/para ratio close to the value corresponding to the local temperature of the gas and dust