Role of adult hippocampal neurogenesis in the antidepressant actions of lactate.

In addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate's antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.

Salt Intake from Processed Meat Products: Benefits, Risks and Evolving Practices.

Currently, there is major consumer concern about dietary salt intake worldwide. However, even with the development of contemporary preservation practices, sodium chloride is still essential in processed meat products. Despite a long history of use, salt is now seriously controversial in food due to health concerns that are mostly related to high blood pressure and cardiovascular risks. Changes in meat processing methods have reduced those potential risks, but different perceptions continue to shape how consumers and society view dietary salt. The current consumer demand for additive-free food, such as the clean-label movement, has renewed consumer willingness for naturalness in food products.

[Improving understanding of the physiological mechanisms of exercise to better treat depression]. / Mieux comprendre les mécanismes physiologiques de l'activité physique pour mieux traiter la dépression.

According to the Swiss Health Survey one in five people will suffer from a major depressive episode at least once during their lifetime. Antidepressants and psychotherapy play a prominent role in patient management. In recent years, many studies have shown that physical activity also reduces depressive symptoms. Among mechanisms involved in the antidepressant effects of exercise, a recent study based on animal models of depression suggests that lactate may contribute to reducing depressive symptoms in response to physical activity. Elucidation of the mechanisms underlying the antidepressant effects of lactate may contribute to identify novel therapeutic targets for the treatment of depression.

L'Enquête suisse sur la santé estime qu'une personne sur cinq souffrira au moins une fois dans sa vie d'un épisode dépressif. Les antidépresseurs, ainsi que la psychothérapie, occupent une place de choix dans la prise en charge des patients. Au cours de ces dernières années, de nombreuses études ont démontré que l'activité physique réduit également les symptômes dépressifs. Parmi les mécanismes impliqués dans les effets antidépresseurs de l'exercice, une étude récente réalisée sur des modèles animaux de dépression suggère que le lactate pourrait contribuer à la réduction des symptômes dépressifs par l'activité physique. L'élucidation des mécanismes qui sous-tendent les effets antidépresseurs de l'activité physique pourrait contribuer à identifier de nouvelles cibles thérapeutiques pour le traitement de la dépression.

An ion transport-independent role for the cation-chloride cotransporter KCC2 in dendritic spinogenesis in vivo.

The neuron-specific K-Cl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in pyramidal neurons, and recent in vitro data suggest that this protein plays a role in the development of dendritic spines. The in vivo relevance of these observations is, however, unknown. Using in utero electroporation combined with post hoc iontophoretic injection of Lucifer Yellow, we show that premature expression of KCC2 induces a highly significant and permanent increase in dendritic spine density of layer 2/3 pyramidal neurons in the somatosensory cortex. Whole-cell recordings revealed that this increased spine density is correlated with an enhanced spontaneous excitatory activity in KCC2-transfected neurons. Precocious expression of the N-terminal deleted form of KCC2, which lacks the chloride transporter function, also increased spine density. In contrast, no effect on spine density was observed following in utero electroporation of a point mutant of KCC2 (KCC2-C568A) where both the cotransporter function and the interaction with the cytoskeleton are disrupted. Transfection of the C-terminal domain of KCC2, a region involved in the interaction with the dendritic cytoskeleton, also increased spine density. Collectively, these results demonstrate a role for KCC2 in excitatory synaptogenesis in vivo through a mechanism that is independent of its ion transport function.

Inactivation of Toxoplasma gondii in dry sausage and processed pork, and quantification of the pathogen in pig tissues prior to production.

Toxoplasma gondii is an important zoonotic foodborne parasite. Meat of infected animals appears to be a major source of infection in Europe. Pork is the most consumed meat in France, with dry sausages well represented. The risk of transmission via consumption of processed pork products is largely unknown, mainly since processing will affect viability but may not entirely inactivate all T. gondii parasites. We investigated the presence and concentration of T. gondii DNA in the shoulder, breast, ham, and heart of pigs orally inoculated with 1000 oocysts (n = 3) or tissue cysts (n = 3) and naturally infected pigs (n = 2), by means of magnetic capture qPCR (MC-qPCR). Muscle tissues of experimentally infected pigs were further used to evaluate the impact of manufacturing processes of dry sausages, including different concentrations of nitrates (0, 60, 120, 200 ppm), nitrites (0, 60, 120 ppm), and NaCl (0, 20, 26 g/kg), ripening (2 days at 16-24 °C) and drying (up to 30 days at 13 °C), by a combination of mouse bioassay, qPCR and MC-qPCR. DNA of T. gondii was detected in all eight pigs, including in 41.7% (10/24) of muscle samples (shoulder, breast and ham) and 87.5% (7/8) of hearts by MC-qPCR. The number of parasites per gram of tissue was estimated to be the lowest in the hams (arithmetic mean (M) = 1, standard deviation (SD) = 2) and the highest in the hearts (M = 147, SD = 233). However, the T. gondii burden estimates varied on the individual animal level, the tissue tested and the parasitic stage used for the experimental infection (oocysts or tissue cysts). Of dry sausages and processed pork, 94.4% (51/54) were positive for T. gondii by MC-qPCR or qPCR, with the mean T. gondii burden estimate equivalent to 31 parasites per gram (SD = 93). Only the untreated processed pork sample collected on the day of production was positive by mouse bioassay. The results suggest an uneven distribution of T. gondii in the tissues examined, and possibly an absence or a concentration below the detection limit in some of them. Moreover, the processing of dry sausages and processed pork with NaCl, nitrates, and nitrites has an impact on the viability of T. gondii from the first day of production. Results are valuable input for future risk assessments aiming to estimate the relative contribution of different sources of T. gondii human infections.

Effects of sodium nitrite reduction, removal or replacement on cured and cooked meat for microbiological growth, food safety, colon ecosystem, and colorectal carcinogenesis in Fischer 344 rats.

Epidemiological and experimental evidence indicated that processed meat consumption is associated with colorectal cancer risks. Several studies suggest the involvement of nitrite or nitrate additives via N-nitroso-compound formation (NOCs). Compared to the reference level (120 mg/kg of ham), sodium nitrite removal and reduction (90 mg/kg) similarly decreased preneoplastic lesions in F344 rats, but only reduction had an inhibitory effect on Listeria monocytogenes growth comparable to that obtained using the reference nitrite level and an effective lipid peroxidation control. Among the three nitrite salt alternatives tested, none of them led to a significant gain when compared to the reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions in rats despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions in rats but the concomitant presence of nitrosyl iron in feces. Except the vegetable stock, other alternatives were less efficient than sodium nitrite in reducing L. monocytogenes growth.

Combination of High-Pressure Treatment at 500 MPa and Biopreservation with a Lactococcus lactis Strain for Lowering the Bacterial Growth during Storage of Diced Cooked Ham with Reduced Nitrite Salt.

We investigated the combined effects of biopreservation and high-pressure treatment on bacterial communities of diced cooked ham prepared with diminished nitrite salt. First, bacterial communities of four commercial brands of diced cooked ham from local supermarkets were characterized and stored frozen. Second, sterile diced cooked ham, prepared with reduced levels of nitrite, was inoculated with two different microbiota collected from the aforementioned commercial samples together with a nisin-producing Lactococcus lactis protective strain able to recover from a 500 MPa high-pressure treatment. Samples were then treated at 500 MPa for 5 min, and bacterial dynamics were monitored during storage at 8 °C. Depending on samples, the ham microbiota was dominated by different Proteobacteria (Pseudomonas, Serratia, Psychrobacter, or Vibrio) or by Firmicutes (Latilactobacillus and Leuconostoc). Applied alone, none of the treatments stabilized during the growth of the ham microbiota. Nevertheless, the combination of biopreservation and high-pressure treatment was efficient in reducing the growth of Proteobacteria spoilage species. However, this effect was dependent on the nature of the initial microbiota, showing that the use of biopreservation and high-pressure treatment, as an alternative to nitrite reduction for ensuring cooked ham microbial safety, merits attention but still requires improvement.

Regulation of dendritic development by BDNF requires activation of CRTC1 by glutamate.

Dendritic growth is essential for the establishment of a functional nervous system. Among extrinsic signals that control dendritic development, substantial evidence indicates that BDNF regulates dendritic morphology. However, little is known about the underlying mechanisms by which BDNF controls dendritic growth. In this study, we show that the MAPK signaling pathway and the transcription factor cAMP response element-binding protein (CREB) mediate the effects of BDNF on dendritic length and complexity. However, phosphorylation of CREB alone is not sufficient for the stimulation of dendritic growth by BDNF. Thus, using a mutant form of CREB unable to bind CREB-regulated transcription coactivator (CRTC1), we demonstrate that this effect also requires a functional interaction between CREB and CRTC1. Moreover, inhibition of CRTC1 expression by shRNA-mediated knockdown abolished BDNF-induced dendritic growth of cortical neurons. Interestingly, we found that nuclear translocation of CRTC1 results from activation of NMDA receptors by glutamate, a process that is essential for the effects of BDNF on dendritic development. Together, these data identify a previously unrecognized mechanism by which CREB and the coactivator CRTC1 mediate the effects of BDNF on dendritic growth.

Cellular mechanisms underlying the regulation of dendritic development by hepatocyte growth factor.

Acquisition of a mature dendritic morphology is critical for neural information processing. In particular, hepatocyte growth factor (HGF) controls dendritic arborization during brain development. However, the cellular mechanisms underlying the effects of HGF on dendritic growth remain elusive. Here, we show that HGF increases dendritic length and branching of rat cortical neurons through activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of MAPK by HGF leads to the rapid and transient phosphorylation of cAMP response element-binding protein (CREB), a key step necessary for the control of dendritic development by HGF. In addition to CREB phosphorylation, regulation of dendritic growth by HGF requires the interaction between CREB and CREB-regulated transcription coactivator 1 (CRTC1), as expression of a mutated form of CREB unable to bind CRTC1 completely abolished the effects of HGF on dendritic morphology. Treatment of cortical neurons with HGF in combination with brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that regulates dendritic development via similar mechanisms, showed additive effects on MAPK activation, CREB phosphorylation and dendritic growth. Collectively, these results support the conclusion that regulation of cortical dendritic morphology by HGF is mediated by activation of the MAPK pathway, phosphorylation of CREB and interaction of CREB with CRTC1.

Monitoring of endogenous nitric oxide exhaled by pig lungs during ex-vivo lung perfusion.

In the context of organ shortage for transplantation, new criteria for better organ evaluation should be investigated. Ex-vivo lung perfusion (EVLP) allows extra-corporal lung re-conditioning and evaluation, under controlled parameters of the organ reperfusion and mechanical ventilation. This work reports on the interest of exhaled gas analysis during the EVLP procedure. After a 1 h cold ischemia, the endogenous gas production by an isolated lung of nitric oxide and carbon monoxide is simultaneously monitored in real time. The exhaled gas is analysed with two very sensitive and selective laser spectrometers developed upon the technique of optical-feedback cavity-enhanced absorption spectroscopy. Exhaled gas concentration measured for an ex-vivo lung is compared to the corresponding production by the whole living pig, measured before euthanasia. On-line measurements of the fraction of nitric oxide in exhaled gas (FENO) in isolated lungs are reported here for the first time, allowing to resolve the respiratory cycles. In this study, performed on 9 animals, FENO by isolated lungs range from 3.3 to 10.6 ppb with a median value of 4.4 ppb. Pairing ex-vivo lung and pig measurements allows to demonstrate a systematic increase of FENO in the ex-vivo lung as compared to the living animal, by a factor of 3 ± 1.2. Measurements of the fraction of carbon monoxide in exhaled gas (FECO) confirm levels recorded during previous studies driven to evaluate FECO as a potential marker of ischemia reperfusion injuries. FECO production by ex-vivo lungs ranges from 0.31 to 2.3 ppm with a median value of 0.8 ppm. As expected, these FECO values are lower than the production by the corresponding whole pig body, by a factor of 6.9 ± 2.7.

Expression of brain-derived neurotrophic factor is not modulated by chronic mild stress in the rat hippocampus and amygdala.

Accumulating evidence supports a role for brain-derived neurotrophic factor (BDNF) in depression. However, most of these studies have been performed in animal models that have a low face validity with regard to the human disease. Here, we examined the regulation of BDNF expression in the hippocampus and amygdala of rats subjected to the chronic mild stress (CMS) model of depression, a paradigm that induces anhedonia, a core symptom of depression. We found that exposure of rats to the CMS paradigm did not modulate BDNF mRNA expression in the hippocampus and amygdala. In addition, chronic administration of imipramine, which reversed CMS-induced anhedonia, did not alter BDNF mRNA expression in these limbic structures.

Beef sausage structure affected by sodium chloride and potassium lactate.

A histological and ultrastructural study was conducted to characterize changes in the muscle fibre structure of three fresh sausage preparations, depending on meat composition, sodium chloride (NaCl) and potassium lactate (K-lactate) contents. After addition of 0.8% and 1.6% NaCl, 65% and 51%, respectively, of the area observed showed well preserved fibres (histological data). The altered regions presented a large disorganization of the myofilaments and a solubilization of the sarcolemma and of the Z lines. K-lactate addition had no marked effects on meat structure. The preparation containing some sheep meat was more sensitive to salt than the others containing only bovine meat. The level of alteration was much lower than those obtained in pork meat in another study. Technological conditions used to modify the internal muscle fibre structure during sausage processing depend on the species used. Therefore, the classification of the sausage preparation to "meat preparation" or "meat product" under the EU regulation (EC) No. 853/2004 (which assign meat preparations to meat if the product has undergone a process insufficient to modify the internal muscle fibre structure of the meat) must be systematically controlled when changing the meat sausage composition.

Selection procedure of bioprotective cultures for their combined use with High Pressure Processing to control spore-forming bacteria in cooked ham.

High Pressure Processing (HPP) and biopreservation can contribute to food safety by inactivation of bacterial contaminants. However these treatments are inefficient against bacterial endospores. Moreover, HPP can induce spore germination. The objective of this study was to select lactic acid bacteria strains to be used as bioprotective cultures, to control vegetative cells of spore-forming bacteria in ham after application of HPP. A collection of 63 strains of various origins was screened for their antagonistic activity against spore-forming Bacillus and Clostridium species and their ability to resist to HPP. Some safety requirements should also be considered prior to their introduction into the food chain. Hence, the selection steps included the assessment of biogenic amine production and antibiotic resistance. No strain produced histamine above the threshold detection level of 50 ppm. From the assessment of antibiotic resistance against nine antibiotics, 14 susceptible strains were kept. Antagonistic action of the 14 strains was then assessed by the well diffusion method against pathogenic or spoilage spore-forming species as Bacillus cereus, Clostridium sp. like botulinum, Clostridium frigidicarnis, and Clostridium algidicarnis. One Lactobacillus curvatus strain and one Lactococcus lactis strain were ultimately selected for their widest inhibitory spectrum and their potential production of bacteriocin. A Lactobacillus plantarum strain was included as control. Their resistance to HPP and ability to regrow during chilled storage was then assessed in model ham liquid medium. Treatments of pressure intensities of 400, 500, and 600 MPa, and durations of 1, 3, 6, and 10 min were applied. After treatment, cultures were incubated at 8 °C during 30 days. Inactivation curves were then fitted by using a reparameterized Weibull model whereas growth curves were modelled with a logistic model. Although the two Lactobacillus strains were more resistant than L. lactis to HPP, the latter was the only strain able to regrow following HPP. The absence of biogenic amine production of this strain after growth on diced cube cooked ham was also shown. In conclusion this L. lactis strain could be selected as representing the best candidate for a promising preservative treatment combining biopreservation and HPP to control spore-forming bacteria in cooked ham.

Brain-derived neurotrophic factor stimulates energy metabolism in developing cortical neurons.

Brain-derived neurotrophic factor (BDNF) promotes the biochemical and morphological differentiation of selective populations of neurons during development. In this study we examined the energy requirements associated with the effects of BDNF on neuronal differentiation. Because glucose is the preferred energy substrate in the brain, the effect of BDNF on glucose utilization was investigated in developing cortical neurons via biochemical and imaging studies. Results revealed that BDNF increases glucose utilization and the expression of the neuronal glucose transporter GLUT3. Stimulation of glucose utilization by BDNF was shown to result from the activation of Na+/K+-ATPase via an increase in Na+ influx that is mediated, at least in part, by the stimulation of Na+-dependent amino acid transport. The increased Na+-dependent amino acid uptake by BDNF is followed by an enhancement of overall protein synthesis associated with the differentiation of cortical neurons. Together, these data demonstrate the ability of BDNF to stimulate glucose utilization in response to an enhanced energy demand resulting from increases in amino acid uptake and protein synthesis associated with the promotion of neuronal differentiation by BDNF.

Effect of added thiamine on the key odorant compounds and aroma of cooked ham.

This study shows that thiamine plays a major role in the formation of three key odorants of cooked ham: 2-methyl-3-furanthiol, 2-methyl-3-methyldithiofuran, and bis(2-methyl-3-furyl)disulphide. Analyses revealed that under identical cooking conditions, the productions of these three aroma compounds increase in a closely intercorrelated way when the dose of thiamine increases. Using a specific 2-methyl-3-furanthiol extraction-quantification method, it was possible to relate the amounts of thiamine added in model cooked hams to the amounts of 2-methyl-3-furanthiol produced in the cooking process. Sensory analyses highlighted the role of thiamine as a precursor of cooked ham aroma.

Defect dynamics in a smectic Grandjean-Cano wedge.

An array of edge dislocation forms spontaneously in a Grandjean-Cano wedge filled by a smectic liquid crystal. In the vicinity of the smectic A to smectic C transition, these defects are visible under the microscope [R. B. Meyer, B. Stebler, and S. T. Lagerwall, Phys. Rev. Lett. 41, 1393 (1978)]. This paper deals with their dynamics under controlled deformation (dilation and compression). First, we characterize several regimes of dislocation mobility occurring with increasing strain epsilon or strain rate epsilon;. We relate these regimes to the interactions between screw and edge dislocations. We also show that screw dislocations give rise to loops of edge dislocations under sufficient strain, which strengthens the model of loop nucleation by helical instability of screw dislocations. Lastly, we discuss several models for the microscopic origin of the interactions between defects.

Identification and origin of odorous sulfur compounds in cooked ham.

The aim of this work was to identify and gain further knowledge on the origin of sulfur compounds present in the volatile fraction of cooked ham, and on their role in the aroma of this product. To this end, we performed analyses by one- and two-dimensional gas chromatography coupled with mass spectrometry, and olfactometry. Among the odorant sulfur compounds identified, three furans present in trace amounts proved to have very intense odours responsible for the "meaty, cooked ham" notes of this pork product. They were 2-methyl-3-furanthiol, 2-methyl-3-(methyldithio)furan and bis(2-methyl-3-furyl) disulphide. Addition of thiamine or cysteine also enabled us to study the effect of these odour precursors on the formation of odorant furans during the cooking of ham. The results revealed a direct link between the thermal degradation of thiamine and the formation of these compounds. By contrast, addition of cysteine in the presence of fructose or xylose did not appreciably increase their production.

Role of salt-inducible kinase 1 in the activation of MEF2-dependent transcription by BDNF.

Substantial evidence supports a role for myocyte enhancer factor 2 (MEF2)-mediated transcription in neuronal survival, differentiation and synaptic function. In developing neurons, it has been shown that MEF2-dependent transcription is regulated by neurotrophins. Despite these observations, little is known about the cellular mechanisms by which neurotrophins activate MEF2 transcriptional activity. In this study, we examined the role of salt-inducible kinase 1 (SIK1), a member of the AMP-activated protein kinase (AMPK) family, in the regulation of MEF2-mediated transcription by the neurotrophin brain-derived neurotrophic factor (BDNF). We show that BDNF increases the expression of SIK1 in primary cultures of rat cortical neurons through the extracellular signal-regulated kinase 1/2 (ERK1/2)-signaling pathway. In addition to inducing SIK1 expression, BDNF triggers the phosphorylation of SIK1 at Thr182 and its translocation from the cytoplasm to the nucleus of cortical neurons. The effects of BDNF on the expression, phosphorylation and, translocation of SIK1 are followed by the phosphorylation and nuclear export of histone deacetylase 5 (HDAC5). Blockade of SIK activity with a low concentration of staurosporine abolished BDNF-induced phosphorylation and nuclear export of HDAC5 in cortical neurons. Importantly, stimulation of HDAC5 phosphorylation and nuclear export by BDNF is accompanied by the activation of MEF2-mediated transcription, an effect that is suppressed by staurosporine. Consistent with these data, BDNF induces the expression of the MEF2 target genes Arc and Nur77, in a staurosporine-sensitive manner. In further support of the role of SIK1 in the regulation of MEF2-dependent transcription by BDNF, we found that expression of wild-type SIK1 or S577A SIK1, a mutated form of SIK1 which is retained in the nucleus of transfected cells, is sufficient to enhance MEF2 transcriptional activity in cortical neurons. Together, these data identify a previously unrecognized mechanism by which SIK1 mediates the activation of MEF2-dependent transcription by BDNF.

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes.

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established.

Effect of nitrite on the odourant volatile fraction of cooked ham.

The aim of this work was to reliably identify the key odour compounds in cooked ham and acquire new knowledge on the role of sodium nitrite on the formation of its aroma. Gas chromatography coupled with mass spectrometry and (or) olfactometry was used. In all, 24 odourants were identified in the volatile fraction of cooked ham. Their main origins are discussed. Orthonasal sniffing of the hams was used to study how these substances contributed to the overall aroma of the product. The aroma of cooked ham is a balance between that of certain sulfur compounds produced during cooking and that of oxidation compounds commonly found in cooked meats. In the absence of nitrite, this balance is disturbed by extensive formation of oxidation compounds that mask the meaty notes induced by the sulfur compounds.