The antidepressant-like effect of Ocimum basilicum in an animal model of depression

We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open ?eld test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.     

The ecdysone inducible gene expression system: unexpected effects of muristerone A and ponasterone A on cytokine signaling in mammalian cells

Inducible gene expression systems in mammalian cells have been shown to be valuable processes to study the specific function of a protein in differentiation, proliferation or survival/apoptosis. Usually, these systems use as inducible reagents, compounds that are thought to be neutral and devoid of physiological or biologically undesirable effects in mammalian cells. We recently used the ecdysone inducible gene expression system in hematopoietic cells and found that the two inducer analogs of ecdysone, muristerone A and ponasterone A, altered the signaling pathways induced by IL-3 in the pro-B cell-line, Ba/F3. Indeed, we showed that these two analogs potentiate the IL-3-dependent activation of the PI 3-kinase/Akt pathway, which could ultimately interfere with the growth, and/or survival of these cells.     

Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons

Inferior olivary neurons (ION) migrate circumferentially around the caudal rhombencephalon starting from the alar plate to locate ventrally close to the floor-plate, ipsilaterally to their site of proliferation. The floor-plate constitutes a source of diffusible factors. Among them, netrin-1 is implied in the survival and attraction of migrating ION in vivo and in vitro. We have looked for a possible involvement of slit-1/2 during ION migration. We report that: (1) slit-1 and slit-2 are coexpressed in the floor-plate of the rhombencephalon throughout ION development; (2) robo-2, a slit receptor, is expressed in migrating ION, in particular when they reach the vicinity of the floor-plate; (3) using in vitro assays in collagen matrix, netrin-1 exerts an attractive effect on ION leading processes and nuclei; (4) slit has a weak repulsive effect on ION axon outgrowth and no effect on migration by itself, but (5) when combined with netrin-1, it antagonizes part of or all of the effects of netrin-1 in a dose-dependent manner, inhibiting the attraction of axons and the migration of cell nuclei. Our results indicate that slit silences the attractive effects of netrin-1 and could participate in the correct ventral positioning of ION, stopping the migration when cell bodies reach the floor-plate.     

Role of chemical and visual cues in food recognition by leatherback posthatchlings (Dermochelys coriacea L)

We raised leatherback posthatchlings in the laboratory for up to 7 weeks to study the role of visual and chemical cues in food recognition and food-seeking behavior. Turtles were reared on a formulated (artificial gelatinous) diet and had no contact with test materials until experiments began. Subjects were presented with visual cues (a plastic jellyfish; white plastic shapes [circle, square, diamond] similar in surface area to the plastic model), chemical cues (homogenates of lion's mane jellyfish, Cyanea capillata; moon jellyfish, Aurelia aurita; and a ctenophore, Ocyropsis sp., introduced through a water filter outflow), and visual and chemical cues presented simultaneously. Visual stimuli evoked an increase in swimming activity, biting, diving, and orientation toward the object. Chemical cues elicited an increase in biting, and orientation into water currents (rheotaxis). When chemical and visual stimuli were combined, turtles ignored currents and oriented toward the visual stimuli. We conclude that both cues are used to search for, and locate, food but that visual cues may be of primary importance. We hypothesize that under natural conditions turtles locate food visually, then, as a consequence of feeding, associate chemical with visual cues. Chemical cues then may function alone as a feeding attractant.     

Engaging neuroscience to advance translational research in brain barrier biology

The delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by brain barriers, of which the most well known are the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier. Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, in the control of cerebral blood flow, and--when barrier integrity is impaired--in the pathology of many common CNS disorders such as Alzheimer's disease, Parkinson's disease and stroke.     

High sero-prevalence of caseous lymphadenitis identified in slaughterhouse samples as a consequence of deficiencies in sheep farm management in the state of Minas Gerais, Brazil

Background

Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.

Results

We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as PMEL17 heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies. One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.

Conclusions

The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.     

Rock-inhabiting fungi originated during periods of dry climate in the late Devonian and middle Triassic

Non-lichenized rock-inhabiting fungi (RIF) are slow-growing melanized ascomycetes colonizing rock surfaces in arid environments. They possess adaptations, which allow them to tolerate extreme abiotic conditions, such as high UV radiations and extreme temperatures. They belong to two separate lineages, one consisting in the sister classes Dothideomycetes and Arthoniomycetes (Dothideomyceta), and the other consisting in the order Chaetothyriales (Eurotiomycetes). Because RIF often form early diverging groups in Chaetothyriales and Dothideomyceta, the ancestors of these two lineages were suggested to most likely be rock-inhabitants. The lineage of RIF related to the Chaetothyriales shows a much narrower phylogenetic spectrum than the lineage of RIF related to Dothideomyceta, suggesting a much more ancient origin for the latter. Our study aims at investigating the times of origin of RIF using a relaxed clock model and several fossil and secondary calibrations. Our results show that the RIF in Dothideomyceta evolved in the late Devonian, much earlier than the RIF in Chaetothyriales, which originated in the middle Triassic. The origin of the chaetothyrialean RIF correlates well with a period of recovery after the Permian-Triassic mass extinction and an expansion of arid landmasses. The period preceding the diversification of the RIF related to Dothideomyceta (Silurian--Devonian) is also characterized by large arid landmasses, but temperatures were much cooler than during the Triassic. The paleoclimate record provides a good explanation for the diversification of fungi subjected to abiotic stresses and adapted to life on rock surfaces in nutrient-poor habitats.     

Age-dependent decrease in adenosine A1 receptor binding sites in the rat brain. Effect of cis unsaturated free fatty acids.

Unsaturated free fatty acids and adenosine operate two neuromodulatory systems with opposite effects on neuronal function. Here, we tested if fatty acids controlled inhibitory adenosine A1 receptors. Arachidonate (AA, 10 microM) decreased the Bmax of an A1 receptor agonist, (R)-[3H]phenylisopropyladenosine (PIA; from 812 to 267 fmol x mg(-1) protein), and antagonist, [3H]1,3-dipropyl-8-cyclopentylxanthine (DPCPX; from 994 to 311 fmol x mg(-1) protein) and decreased the Kd of [3H]PIA (from 1.20 to 0.57 nM) binding to brain membranes of young adult rats (2 months old), these effects being mimicked by other cis but not trans unsaturated or saturated fatty acids. AA (10 microM) increased the potency of the A1 receptor agonist, 2-chloroadenosine to inhibit hippocampal synaptic transmission in young adult rats (EC50 decreased from 337 to 237 nM), which may constitute a safety feedback mechanism to control AA-induced neurotoxicity. Upon aging, there were increased free fatty acid levels and a concomitant decreased density of A1 receptors. This was more marked in hippocampal nerve terminals of aged rats (24 months old) and may be the determinant factor contributing to the lower potency of 2-choloroadenosine in aged rats (EC50 = 955 nM), in spite of the decreased Kd of PIA binding upon aging. The effects of AA on A1 receptor binding were attenuated upon aging, AA being devoid of effects in aged rats. Accordingly, AA (10 microM) failed to modify the potency of 2-choloroadenosine in aged rats (EC50 = 997 nM). However, albumin, which quenches free fatty acids, increased A1 receptor density by 65% and 2-chloroadenosine potency (EC50 = 703 nM) in aged rats, suggesting that the increased fatty acids levels in aged rats may contribute to the decreased potency of A1 receptor agonists in aged rats. Also, the observed saturation of the control by AA of A1 receptors may contribute to the decreased adaptability of neuromodulation to different firing conditions in aged rats.     

Models of cardiac electromechanics based on individual hearts imaging data Image-based electromechanical models of the heart

Current multi-scale computational models of ventricular electromechanics describe the full process of cardiac contraction on both the micro- and macro- scales including: the depolarization of cardiac cells, the release of calcium from intracellular stores, tension generation by cardiac myofilaments, and mechanical contraction of the whole heart. Such models are used to reveal basic mechanisms of cardiac contraction as well as the mechanisms of cardiac dysfunction in disease conditions. In this paper, we present a methodology to construct finite element electromechanical models of ventricular contraction with anatomically accurate ventricular geometry based on magnetic resonance and diffusion tensor magnetic resonance imaging of the heart. The electromechanical model couples detailed representations of the cardiac cell membrane, cardiac myofilament dynamics, electrical impulse propagation, ventricular contraction, and circulation to simulate the electrical and mechanical activity of the ventricles. The utility of the model is demonstrated in an example simulation of contraction during sinus rhythm using a model of the normal canine ventricles.