Tau hyperphosphorylation is one hallmark of Alzheimer's disease (AD) pathology. Pharmaceutical companies have thus developed kinase inhibitors aiming to reduce tau hyperphosphorylation. One obstacle ...in screening for tau kinase inhibitors is the low phosphorylation levels of AD-related phospho-epitopes in normal adult mice and cultured cells. We have shown that hypothermia induces tau hyperphosphorylation in vitro and in vivo. Here, we hypothesized that hypothermia could be used to assess tau kinase inhibitors efficacy. Hypothermia applied to models of biological gradual complexity such as neuronal-like cells, ex vivo brain slices and adult non-transgenic mice leads to tau hyperphosphorylation at multiple AD-related phospho-epitopes. We show that Glycogen Synthase Kinase-3 inhibitors LiCl and AR-A014418, as well as roscovitine, a cyclin-dependent kinase 5 inhibitor, decrease hypothermia-induced tau hyperphosphorylation, leading to different tau phosphorylation profiles. Therefore, we propose hypothermia-induced hyperphosphorylation as a reliable, fast, convenient and inexpensive tool to screen for tau kinase inhibitors.
Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a ...therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid content depends on nutritional intake, a readily manipulable environmental factor. Here, we report a postmortem analysis of fatty acid profile by gas chromatography in the brain cortex of human patients (12 PD patients and nine Controls) as well as in the brain cortex of monkeys (four controls, five drug-naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid profile of cerebral cortex tissue was similar between PD patients and Controls and was not correlated with age of death, delay to autopsy or brain pH. Levodopa administration in MPTP monkeys increased arachidonic acid content (+7%;
P
<
0.05) but decreased docosahexaenoic acid concentration (−15%;
P
<
0.05) and total
n
−
3:
n
−
6 polyunsaturated fatty acids ratio (−27%;
P
<
0.01) compared to drug-naive MPTP animals. Interestingly, PD patients who experienced motor complications to levodopa had higher arachidonic acid concentrations in the cortex compared to Controls (+13.6%;
P
<
0.05) and to levodopa-treated PD patients devoid of motor complications (+14.4%;
P
<
0.05). Furthermore, PD patients who took an above-median cumulative dose of levodopa had a higher relative amount of saturated fatty acids but lower monounsaturated fatty acids in their brain cortex (
P
<
0.01). These results suggest that changes in brain fatty acid relative concentrations are associated with levodopa treatment in PD patients and in a non-human primate model of parkinsonism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As ...Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser(202)/Thr(205)), PHF-1 (Ser(396)/Ser(404)) and AT180 (Thr(231)) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several anesthetics have been reported to suppress the transcription of a number of genes, including Arc, also known as Arg3.1, an immediate early gene that plays a significant role in memory ...consolidation. The purpose of this study was to explore the mechanism of anesthesia-mediated depression in Arc gene and protein expression. Here, we demonstrate that isoflurane or propofol anesthesia decreases hippocampal Arc protein expression in rats and mice. Surprisingly, this change was secondary to anesthesia-induced hypothermia. Furthermore, we confirm in vivo and in vitro that hypothermia per se is directly responsible for decreased Arc protein levels. This effect was the result of the decline of Arc mRNA basal levels following inhibition of ERK/MAPK by hypothermia. Overall, our results suggest that anesthesia-induced hypothermia leads to ERK inhibition, which in turns decreases Arc levels. These data give new mechanistic insights on the regulation of immediate early genes by anesthesia and hypothermia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Vaccination has been developed over the years to counter coccidiosis; however, its effectiveness varies, and it is difficult to exploit due in particular to the young age of chickens at ...slaughter. Cashew nutsell liquid (CNSL) supplements have shown beneficial effects on growth performance and anticoccidial effects in Eimeria-challenged broilers. However, CNSL effects during an Eimeria infection in vaccinated chickens against coccidiosis need to be determined especially for organic production. Broilers vaccinated against coccidiosis were housed in pens and received one of the following treatments: 1) non-infected, non-treated (blank control); 2) infected, non-treated (negative control); 3) infected, nibarbazin/monensin shuttle program (positive control); 4) infected, Calica+ (CNSL-based formulation). Eimeria infection was induced by an oral administration of 200,000 sporulated oocysts of mixed Eimeria species harvested from field isolates. The trial was performed with 8 pens of 45 birds per treatment. Performance data and oocyst counts were analyzed by a mixed model including treatment as fixed effect and pen as random effect. Intestinal lesion scores were analyzed by category analyses. Calica+ improved average daily gain (ADG) (+7.4%, P < 0.05) and showed a trend to reduce feed conversion ratio (FCR) (−1.8%, P < 0.07) during the overall growing period (days 0–35), compared to infected and untreated broilers. Birds fed Calica+ also showed higher ADG than birds on nibarbazin/monensin shuttle program (+7.2%, P < 0.05). Calica+ did not change levels of oocysts per gram of feces (OPG) at Eimeria excretion peak (6 days after inoculation) but it showed a trend to reduce the Eimeria tenella intestinal lesion scores (p< 0.0685). In summary, the CNSL-based formulation Calica+ showed beneficial growth performance and anticoccidial effects in vaccination conditions against coccidiosis. This organic feed additive could be involved in an anticoccidiosis strategy that includes vaccination.
Abstract
One of the most common insects in poultry houses is the mealworm Alphitobius diaperinus, also known as the darkling beetle. Immature (larvae) and adults feed on seeds spilled on the ground ...or from poultry droppings. In addition to structural damage, this insect can also be a vector of diseases that can affect birds. In addition, the indigestible shell of the insect can cause digestion problems for birds, and thus affect the profitability of production. It is considered impossible to eliminate the populations of mealworms, and in organic poultry production, the control options are limited. The mycoinsecticide BioCeres WP, based on the fungus Beauveria bassiana, and which controls aphids, has been proposed to control the mealworm A. diaperinus in chicken barns. 450 adult mealworms from a commercial chicken barn were randomly distributed in 9 containers (1 m2) containing 10 cm of wood shavings litter and chicken feed. BioCeres WP was applied by spraying two applications of 40 ml of 10 g/L solution (representing 4 x 10^9 conidia per m2 per application). Mealworms were housed during a broiler batch at the chicken barn they were harvested from and received one of the following treatments: 1) control, water spraying; 2) BioCeres WP treatment. 3 repetitions for control and 6 for BioCeres WP were performed. BioCeres WP increased the mortality rate of mealworms (+101%, P < 0.02; 17.8% vs. 8.6%), compared to untreated mealworms, 28 days after treatment. Mortality rates were affected from day 14 until day 28 after treatment. A trial using 640 broilers in 32 pens revealed no adverse effect on growth performance or health. In summary, BioCeres WP could be involved in a biological strategy to control the mealworm Alphitobius diaperinus in chicken barns.
Vaccination has been developed over the years to counter coccidiosis; however, its effectiveness varies, and it is difficult to exploit due in particular to the young age of chickens at slaughter. ...Cashew nutsell liquid (CNSL) supplements have shown beneficial effects on growth performance and anticoccidial effects in Eimeria-challenged broilers. However, CNSL effects during an Eimeria infection in vaccinated chickens against coccidiosis need to be determined especially for organic production. Broilers vaccinated against coccidiosis were housed in pens and received one of the following treatments: 1) non-infected, non-treated (blank control); 2) infected, non-treated (negative control); 3) infected, nibarbazin/monensin shuttle program (positive control); 4) infected, Calica+ (CNSL-based formulation). Eimeria infection was induced by an oral administration of 200,000 sporulated oocysts of mixed Eimeria species harvested from field isolates. The trial was performed with 8 pens of 45 birds per treatment. Performance data and oocyst counts were analyzed by a mixed model including treatment as fixed effect and pen as random effect. Intestinal lesion scores were analyzed by category analyses. Calica+ improved average daily gain (ADG) (+7.4%, P < 0.05) and showed a trend to reduce feed conversion ratio (FCR) (-1.8%, P < 0.07) during the overall growing period (days 0-35), compared to infected and untreated broilers. Birds fed Calica+ also showed higher ADG than birds on nibarbazin/monensin shuttle program (+7.2%, P < 0.05). Calica+ did not change levels of oocysts per gram of feces (OPG) at Eimeria excretion peak (6 days after inoculation) but it showed a trend to reduce the Eimeria tenella intestinal lesion scores (p< 0.0685). In summary, the CNSL-based formulation Calica+ showed beneficial growth performance and anticoccidial effects in vaccination conditions against coccidiosis. This organic feed additive could be involved in an anticoccidiosis strategy that includes vaccination.
One of the most common insects in poultry houses is the mealworm Alphitobius diaperinus, also known as the darkling beetle. Immature (larvae) and adults feed on seeds spilled on the ground or from ...poultry droppings. In addition to structural damage, this insect can also be a vector of diseases that can affect birds. In addition, the indigestible shell of the insect can cause digestion problems for birds, and thus affect the profitability of production. It is considered impossible to eliminate the populations of mealworms, and in organic poultry production, the control options are limited. The mycoinsecticide Bi°Ceres WP, based on the fungus Beauveria bassiana, and which controls aphids, has been proposed to control the mealworm A. diaperinus in chicken barns. 450 adult mealworms from a commercial chicken barn were randomly distributed in 9 containers (1 m2) containing 10 cm of wood shavings litter and chicken feed. Bi°Ceres WP was applied by spraying two applications of 40 ml of 10 g/L solution (representing 4 x 10^9 conidia per m2 per application). Mealworms were housed during a broiler batch at the chicken barn they were harvested from and received one of the following treatments: 1) control, water spraying; 2) Bi°Ceres WP treatment. 3 repetitions for control and 6 for Bi°Ceres WP were performed. Bi°Ceres WP increased the mortality rate of mealworms (+101%, P < 0.02; 17.8% vs. 8.6%), compared to untreated mealworms, 28 days after treatment. Mortality rates were affected from day 14 until day 28 after treatment. A trial using 640 broilers in 32 pens revealed no adverse effect on growth performance or health. In summary, Bi°Ceres WP could be involved in a biological strategy to control the mealworm Alphitobius diaperinus in chicken barns.
Abstract
Development of natural alternatives to drugs is necessary for the poultry industry not only for organic production, but also for limiting drug resistance and for complying with upcoming ...regulations. Two pen trials were conducted to evaluate the effect of Calica+, an activated vegetal oil from cashew nut shell liquid (CNSL), on broiler performance and on coccidiosis in different conditions. The first trial was conducted in Eimeria vaccination conditions with commercial Coccivac-B52. The second one was realized in Eimeria challenge conditions, induced by an oral administration of 200,000 sporulated oocysts of mixed Eimeria species harvested from field isolates. In Eimeria vaccination conditions trial, Calica+ improved average daily gain (ADG) (+4.5%, P < 0.05) during the overall growing period and decreased levels of oocysts per gram of feces (OPG) (−44.1%, P < 0.05), at Eimeria excretion peak (days 17–20), compared to untreated broilers. However, no significant effect of Calica+ on Eimeria intestinal lesions was observed. Overall ADG in Calica+-treated birds was not significantly different compared to nicarbazin-monensin anticoccidial medication (P = 0.8362) but showed higher feed conversion ratio (FCR; +6.0%, P < 0.05). In Eimeria challenge conditions trial, Calica+ feeding treatment improved ADG after infection, during the period from d20 to d36 of age (+4.4%, P < 0.05) compared to untreated birds. Compared with nicarbazin-monensin medication, Calica+-treated birds showed higher FCR (+3.5%, P < 0.05), but comparable ADG (P = 0.3145). Interestingly, birds fed the treatment with Calica+ showed a trend of increased plasmatic levels of IL-1ß compared to untreated broilers (+25.6%, P = 0.0676), suggesting an immune activation as a potential mechanism of action for Calica+. In summary, Calica+ showed beneficial growth performance and anticoccidial effects in these two different trial conditions. This feed additive could be involved in a strategy to reduce the use of anticoccidial medication in broiler production.
Abstract To investigate potential dietary risk factors of Alzheimer’s disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 ...polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-β (Aβ) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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