The etiology of Alzheimer's disease (AD) is poorly understood. A growing body of literature suggests that amyloid beta oligomers (AβO) as the root cause of this disease. Here, we describe new translational in vitro and in vivo models of AD, induced by minute amount of in-house preparation of human AβO.AβO were reproducibly prepared from human Aβ 1-42 monomers. Rodent primary neurons were used to assess the neurotoxic activities of AβO in vitro and elderly wild-type mice administered by a single intracerebral injection AβO in vivo.The oligomeric preparations were characterized by SDS-page, electron microscopy and dot-plot tests. In vitro, AβO induced a dose-dependent neurodegeneration on rodent primary neurons based on various read-outs. Interestingly, neurotoxicity was greater with AβO than fibrillar Aβ, while Aβ monomers did not induce any neuronal damage. AβO-induced neurotoxicity was significantly attenuated by brain-derived neurotrophic factor (BDNF). In vivo, a single intracerebral microinjection of AβO in 18-month-old wild-type mice, led to a significant memory impairment, synaptic loss in hippocampus and increased secretion of brain proinflammatory cytokines 15 days post administration. Moreover, the memory deficits were significantly reversed with Donepezil used as reference drug.In conclusion, we characterized new tools for drug screening based on the soluble AβO hypothesis of AD. In vivo, this new non-inherited Alzheimer model can be used both to evaluate disease modifying and symptomatic drugs. Finally, these models are also valuable tools to understand the mechanisms underlying AD.

OBJECTIVES:The green seaweed Ulva sp. contains a large amount of ulvans, a family of sulphated polysaccharides. The present study was designed to investigate in rats the antidepressant- and anxiolytic-like effects of a hydrophilic extract of Ulva sp. (MSP) containing about 45% of ulvans. METHODS:After a 14-day administration of MSP at doses of 10, 20 and 40 mg/kg/day, 48 and 60 male adult Wistar rats were respectively tested in the elevated plus-maze (EPM) and the forced swimming test (FST). In the FST, MSP effects were compared to the reference antidepressant drug imipramine (IMI) (10 mg/kg/day). Acute and sub-chronic toxicities of the extract were also assessed in male and female rats following OECD guidelines. RESULTS:MSP treatment did not modify anxiety-related behaviour in the EPM. In contrast, MSP induced a dose-dependent reduction of immobility behaviour in the FST. At the highest tested dose of 40 mg/kg, MSP displayed a significant antidepressant-like effect similar to IMI. MSP did not modify the exploratory behaviour of rats in the open field test and did not produce any toxic effect. DISCUSSION:MSP may potentially represent a good adjunct or alternative to existing antidepressant therapeutics. Further studies are necessary to confirm the mechanism of action of MSP and its modulation of brain functioning.

Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

The human body is constantly exposed to the risk of traumatic lesions. ROQUETTE Schizochytrium sp. (SCs) is a marine microalgae containing large amounts of health-valuable nutrients, more particularly polyunsaturated fatty acids such as docosahexaenoic acid. SCs was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-O-tetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered after incisional wound healing of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of SCs had significant effects on macroscopic score of skin inflammation. It had also efficient effect on healing process and duration of wound healing with a dose-response by oral administration and a maximal effect observed from the lowest to the highest dose by topical application. These findings suggest that administration of SCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

Taichi Goto, Bunkyo-ku, Tokyo, Japan , Nao Tamai, Bunkyo-ku, Tokyo, Japan , Gojiro Nakagami, Bunkyo-ku, Tokyo, Japan , Masayuki Hirokawa, Chiyoda-ku, Tokyo, Japan , Ayumi Naito, Fujisawa-city, Kanagawa, Japan , Kazuo Takahashi, Fujisawa-city, Kanagawa, Japan , Junichi Umemoto, Fujisawa-city, Kanagawa, Japan , Ayumi Amemiya, Bunkyo-ku, Tokyo, Japan , Aya Kitamura, Bunkyo-ku, Tokyo, Japan , Yuiko Koyano, Bunkyo-ku, Tokyo, Japan , Hiromi Sanada, Bunkyo-ku, Tokyo, Japan

The human body is constantly exposed to the risk of traumatic lesions. Chlorella is a green microalgae enriched with nutrients, vitamins, minerals and chlorophyll. In some communities, Chlorella is a traditional medicinal plant used for the management of inflammation-related diseases. ROQUETTE Chlorella sp. (RCs) was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-Otetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered by topical application after scarification of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of RCs had significant effects on macroscopic score of skin inflammation with an efficient effect on microscopic score with cutaneous application. The microalgae had also efficient effect on healing process and duration of wound healing for both administration routes and particularly at the two highest doses of RCs. These findings suggest that administration of RCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

In the last ten years, cocoa and bitter chocolate with a high content of cocoa have received much attention due to their significant polyphenol contents, and thus, have been recognized as significant sources of phytochemicals with healthful effects. Increasing evidence from experimental preclinical and clinical studies using cocoa polyphenolic extracts or dark chocolate suggest an important role for these high-flavanol-containing products in various human pathologies. In fact, cocoa's polyphenols are susceptible to induce stimulant, relaxant, euphoriant, tonic and antidepressant effects. This article reviews the various cocoa's flavanols, aiming to establish their implications on mood state, particularly on depression, a major public health problem affecting about 12 percent of the world population.

The aim of the present study was to investigate the effects of long-term intervention with oligofructose-enriched inulin on behavioral cognitive, and visuomotor coordination in rats. Three-month-old male and female rats were randomly distributed into two groups receiving either a diet with 10% oligofructose-enriched inulin (SYN1) or a standard diet tested at 12, 18 and 24 months of age. Rats supplemented with SYN1 showed age- and sex-related improvements in spatial learning abilities, depression, anxiety, and visuomotor speed more prominent at 12 and 18 months. These results suggest that long-term intervention with SYN1 can improve cognitive and emotional aspects of aging.

The aim of the present study was to investigate the protective effects of the dextrin NUTRIOSE (R) 6 (Dex) on colonic inflammation. Five percent of Dex or Glucose (Glu) diets were administered for 2 weeks to Wistar male rats prior to colitis induction with 1 mg of TNBS (2,4,6-Trinitrobenzenesulfonic acid) or 20% ethanol (vehicle). An aversive light stimulus avoidance test (ALSAT) was performed to assess the cognitive performances of rats that are correlated to pain. Growth, food intake and biological parameters as caecal wall thickness, enzyme activities, short chain fatty acid content were investigated Macro and microscopic scores of colonic inflammation of each treatment groups were compared. The results suggest that Dex prevents colonic inflammation induced by ethanol and TNBS administrations and have positive consequences on cogmtive impairments.

A new animal model of travelers’ diarrhea has been developed by infecting rats orally with a strain of enterotoxigenic Escherichia coli in order to assess the efficacy of three probiotic formulations for the prevention of travelers’ diarrhea. Five groups of six rats were given daily (by oral gavage) either a placebo (negative and positive control groups), the suspension of bacterial probiotics called FF1, the yeast probiotic Saccharomyces boulardii , or a combination of both, called Protecflor TM . After 14 days of treatment, all groups except the negative control one were infected by oral administration of E. coli . Body temperature, body weight, food and water consumption, stools consistency, behavior, and cytokines secretion were disturbed following E. coli infection. Probiotics-treated groups generally displayed less-pronounced symptoms, the combination of probiotics Protecflor TM being the most effective.

The effects of Acticoa powder on prostate carcinogenesis were investigated using the N-methylnitrosourea and testosterone propionate prostate tumor model. Sixty male Wistar-Unilever rats were randomly divided in four groups of 15 rats: one control group not induced but treated with vehicle (not induced+vehicle) and three chemo-induced groups. Two weeks before prostate tumor induction and then throughout the experiment, chemo-induced rats were orally treated with Acticoa powder at 24 (chemo-induced+Acticoa powder24) or 48 (chemo-induced+Acticoa powder48) mg/kg or with vehicle (chemo-induced+vehicle), daily from Monday to Friday. Survival, body weight, food and water consumption were recorded throughout the experiment. Six rats per group were randomly killed 9 months after the prostate tumor induction for histopathological analysis of prostates. A reduction in the incidence of prostate tumors was observed for the chemo-induced+Acticoa powder48-treated group in comparison with the chemo-induced+vehicle-treated group and no tumors were observed in the chemo-induced+Acticoa powder24-treated group as in the not induced+vehicle-treated group after 9 months. The nine remaining rats per group were maintained in a long-term survival study. The life span of the chemo-induced+Acticoa powder24-treated group was significantly increased in comparison with the chemo-induced+Acticoa powder48 and the chemo-induced+vehicle-treated groups, close to the one of the not induced+vehicle-treated group. A significant reduction in the incidence of prostate tumors was also observed for the chemo-induced+Acticoa powder24 and chemo-induced+Acticoa powder48-treated groups in comparison with the chemo-induced+vehicle-treated group. In conclusion, Acticoa powder at 24 mg/kg protected rats from prostate carcinogenesis when chronically given before the initiation and promotion phases of induction.

Ageing is associated with changes in physiology and morphology; nutritional strategies to decrease morbidity and to prolong life are of high interest. The aim of the study was to investigate the effects of lifelong supplementation with an oligofructose-enriched inulin on morphological and biological markers and lifespan in male and female rats. Male and female rats, age 3 months, were randomised into two groups to receive either a diet with 10 % of an oligofructose-enriched inulin (Synergy 1) or a standard diet (control) for 27 months. The rats were weighed every 2 weeks and their food intake was evaluated on four successive days every 4-6 weeks. Samples were taken at 12, 18 and 24 months of age. During the whole intervention period, male rats receiving Synergy 1 (SYN1-M) displayed lower body weight, cholesterol and plasma triacylglycerolaemia compared with the controls (Cont-M). The survival rate at 24 months of age of SYN1-M rats was 35.3 % greater than that of Cont-M rats. In female rats, the Synergy 1 supplementation (SYN1-F) group also reduced body weight, cholesterol and triacylglycerolaemia levels, but results were less consistent over the experiment. The survival rate at 24 months of age in SYN1-F rats was 33.3 % greater compared with that of the control (Cont-F) group. To conclude, lifelong intervention with Synergy 1 improved biological markers during ageing and survival rate (lifespan) of rats.

Garum Armoricum (R) (GA), a compound rich in polyunsaturated fatty acids, free amino acids, small peptides, vitamins and minerals, was evaluated on two fear-related assays in rats. GA and diazepam (DZP) increased entries into open arms relative to placebo, as well as percentage of open arm entries in the elevated plus-maze test. In a similar fashion, all drugged groups spent more time inside the open arms and less time inside the enclosed arms. After a two-day period of conditioned avoidance learning of an aversive bright light, GA and vehicle groups successfully discriminated the active from the inactive lever. On the initial day of acquisition, GA and piracetam (PIR) groups achieved successful discrimination though the control group did not. These results indicate that GA may have anxiolytic-like effects without causing learning deficiencies. These psychotropic properties of GA may be due to the synergistic action of its active constituents.

The anxiolytic- and antidepressant-like effects of Garum Armoricum (R) (GA), a protein autolysate from the blue ling fish, were studied in male Wistar rats using the conditioned defensive burying (CDB) and the forced swimming (FST) tests, respectively. In the CDB, all doses of GA (25,50 and 100 mg/kg, PO) decreased the global score of anxiety and the latency of the first approach towards the probe after shock, in a similar way to diazepam (DZP) at the dose of 3 mg/kg, PO. But unlike DZP, the latency before touching again the probe after shock was not significantly reduced by GA. In the FST the two higher doses of GA (15 and 45 mg/kg PO) reduced immobility time in a similar way to imipramine (IMI) at the dose of 20 mg/hg, PO. But unlike IMI, GA did not reduce open-field activity and, unlike DZA did not cause a place preference to develop. These results indicate the potential anxiolytic- and antidepressant-like properties of GA in the absence of any change in cerebral activation and dependence. These psychotropic properties of GA may be due to the synergistic action of its active constituents.

Numerous studies have indicated that increased vulnerability to oxidative stress may be the main factor involved in functional declines during normal and pathological ageing, and that antioxidant agents, such as polyphenols, may improve or prevent these deficits. We examined whether 1-year administration of a cocoa polyphenolic extract (Acticoa powder), orally delivered at the dose of 24 mg/kg per d between 15 and 27 months of age, affects the onset of age-related cognitive deficits, urinary free dopamine levels and lifespan in old Wistar-Unilever rats. Acticoa powder improved cognitive performances in light extinction and water maze paradigms, increased lifespan and preserved high urinary free dopamine levels. These results suggest that Acticoa powder may be beneficial in retarding age-related brain impairments, including cognitive deficits in normal ageing and perhaps neurodegenerative diseases. Further studies are required to elucidate the mechanisms of cocoa polyphenols in neuroprotection and to explore their effects in man.

Glycaemic responses to the dextrin NUTRIOSE 6 (Dex) and the MALTISORB maltitol (Mal) have been studied previously but their effects on vigilance and cognitive performances are still not known. The present study assesses dose-related glycaemic responses following Dex administration and the hypothesis that Dex and Mal could modulate the glycaemic response, improve vigilance under stress conditions and improve cognitive performances in rats. The glycaemic responses following Dex and corn syrup GLUCIDEX IT 21 (CoS) solutions at 0.3, 0.5 and 1.0 g/kg body weight administered by oral administration (experiment 1) and glycaemic responses to three cereal bars (standard (CoS), Dex or Dex/Mal bar) (experiment 2) were evaluated. Rats having eaten cereal bars were submitted to vigilance and aversive light stimulus avoidance conditioning tests to assess their vigilance and cognitive performances. The first experiment showed that the glycaemic response to both products is dose-related and that CoS induced a glycaemic response three times higher than the Dex response. The second experiment showed the same glycaemic response for the three cereal bar-treated rats. Yet, an increase in the vigilance of Dex/Mal-treated rats as well as a better discrimination between two levers in the cognitive test for Dex- and Dex/Mal-treated rats were noticed. These results suggest that the glycaemic response is not the only factor to be considered in predicting the efficiency of a food ingredient on vigilance and cognitive performances: these behaviours are improved after Dex- and Mal-prepared cereal bar ingestion whereas the glycaemic response does not differ from the CoS-prepared bar.

Depression is a major public health problem affecting about 12% of the world population. Drugs exist but they have many side effects. In the last few years, natural substances (e.g. flavonoids) have been tested to cure such disorders. Cocoa polyphenolic extract is a complex compound prepared from non-roasted cocoa beans containing high levels of flavonoids. The antidepressant-like effect of cocoa polyphenolic extract was evaluated using the forced swimming test in rats. Cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days, although no change of motor dysfunction was observed with the two doses tested in the open field. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the assumption that the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test model is specific. Further, it can be speculated that this effect might be related to its content of active polyphenols.

Plant extracts are useful in the management of benign prostatic hyperplasia (BPH). This study investigates whether ACTICOA (Barry Callebaut France, Louviers, France) powder (AP), a cocoa polyphenolic extract, could prevent prostate hyperplasia induced by testosterone propionate (TP) in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one negative control group receiving subcutaneous injections of corn oil and treated with vehicle and three groups injected subcutaneously with TP and treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments were given orally and started 2 weeks before the induction of prostate hyperplasia. The influence of TP and AP on body weights and food and water consumption of rats was examined. On day 36, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumption, while AP at both doses tested reduced significantly these differences. TP significantly increased prostate size ratio (P < .001), and this induced increase was significantly inhibited in AP-treated rats in comparison with positive controls (P < .001) in a dose-dependent manner. We conclude that AP can prevent TP-induced prostate hyperplasia and therefore may be beneficial in the management of BPH.