ε-Viniferin Decreases Amyloid Deposits With Greater Efficiency Than Resveratrol in an Alzheimer's Mouse Model.

In a previous study, we showed that viniferin decreased amyloid deposits and reduced neuroinflammation in APPswePS1dE9 transgenic mice between 3 and 6 months of age. In the present study, wild type and APPswePS1dE9 transgenic mice were treated from 7 to 11 or from 3 to 12 months by a weekly intraperitoneal injection of either 20 mg/kg viniferin or resveratrol or their vehicle, the polyethylene glycol 200 (PEG 200). The cognitive status of the mice was evaluated by the Morris water maze test.

Chronic intraperitoneal injection of polyethylene glycol 200 in mice induces hippocampal neuroinflammation.

treatment of hydrophobic substances requires the use of organic solvents, which are often toxic. Consequently, polyethylene glycols (PEGs), which are considered as nontoxic, have been widely used for many years in chemistry and biology. We used PEG 200, which was administrated by intraperitoneal (i.

Natural stilbenes effects in animal models of Alzheimer's disease.

Alzheimer's disease is one of the most frequent neurodegenerative diseases. This pathology is characterized by protein aggregates, mainly constituted by amyloid peptide and tau, leading to neuronal death and cognitive impairments. Drugs currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic therapies.

Trans ε viniferin decreases amyloid deposits and inflammation in a mouse transgenic Alzheimer model.

As Alzheimer's disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice.

Natural polyphenols effects on protein aggregates in Alzheimer's and Parkinson's prion-like diseases.

Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for Alzheimer's disease, α-synuclein and synphilin-1 for Parkinson's disease.

Blood Inflammatory Mediators and Cognitive Decline in Alzheimer's Disease: A Two Years Longitudinal Study.

Peripheral inflammatory processes are involved in Alzheimer's disease (AD). We aimed to determine whether plasma inflammatory mediator levels at diagnosis are associated with cognitive decline through a 2-year follow-up in AD patients. Patients (n = 109, mean age 79.

Trans ε-viniferin is an amyloid-β disaggregating and anti-inflammatory drug in a mouse primary cellular model of Alzheimer's disease.

Alzheimer's disease (AD) is marked by several cellular and molecular damage. Therefore, the therapeutic interest of multi-target molecules is increasingly justified. Polyphenols presenting multiple pharmacological effects would be more efficient.

Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice.

Background: Current evidence suggests a central role for autophagy in many neurodegenerative diseases including Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Furthermore, it is well admitted that inflammation contributes to the progression of these diseases. Interestingly, crosstalks between autophagy and inflammation have been reported in vitro and at the peripheral level such as in Crohn's disease.

Longitudinal follow-up of autophagy and inflammation in brain of APPswePS1dE9 transgenic mice.

Background: In recent years, studies have sought to understand the mechanisms involved in the alteration of autophagic flux in Alzheimer's disease (AD). Alongside the recent description of the impairment of lysosomal acidification, we wanted to study the relationships between inflammation and autophagy, two physiological components deregulated in AD. Therefore, a longitudinal study was performed in APPswePS1dE9 transgenic mice at three, six and twelve months of age.

Involvement of interleukin-1β in the autophagic process of microglia: relevance to Alzheimer's disease.

Background: Autophagy is a major pathway of protein and organelle degradation in the lysosome. Autophagy exists at basal constitutive level and can be induced as a defense mechanism under stress conditions. Molecular relationships between autophagy and inflammation at the periphery were recently evidenced, highlighting a role of autophagy in the regulation of inflammation.

Dissociation of Akt/PKB and ribosomal S6 kinase signaling markers in a transgenic mouse model of Alzheimer's disease.

Previous studies demonstrated that the PKR (double-stranded RNA-activated protein kinase) pathway was activated while the mTOR (mammalian target of rapamycin) pathway was inhibited in Alzheimer's disease (AD). Here, we analysed upstream and downstream factors of mTOR in brain of APP(SL)/PS1 KI mice displaying a massive neuronal loss in hippocampus. While mTOR levels were not modified, we found a great activation of Akt with a robust accumulation of P-Akt((T308)) in non-apoptotic neurons at 6 months of age.

Regulation of initiation factors controlling protein synthesis on cultured astrocytes in lactic acid-induced stress.

The goals of this work were first to assess whether the lactic acidosis observed in vivo in ischemia may by itself explain the inhibition of protein synthesis described in the literature and second to study the factors controlling the initiation of protein synthesis under lactic acid stress. Primary rat astrocyte cultures exposed to pH 5.25 underwent cell death and a strong inhibition of protein synthesis assessed by [3H]methionine incorporation, which was solely due to acidity of the extracellular medium and was not related to lactate concentrations.

Fluoro-Jade B staining as useful tool to identify activated microglia and astrocytes in a mouse transgenic model of Alzheimer's disease.

Fluoro-Jade B is known as a high affinity fluorescent marker for the localization of neuronal degeneration during acute neuronal distress. However, one study suggested that fluoro-Jade B stains reactive astroglia in the primate cerebral cortex. In this study, we analyzed the staining of fluoro-Jade B alone or combined with specific markers for detection of glial fibrillary acidic protein (GFAP) or activated CD68 microglia in the double APP(SL)/PS1 KI transgenic mice of Alzheimer's disease (AD), which display a massive neuronal loss in the CA1 region of the hippocampus.

Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer's disease.

In this study, brain gangliosides of different transgenic mouse models of Alzheimer's disease (AD) were analyzed and compared with age-matched wild-type mice. Gangliosides were analyzed in cerebral cortex, a region with extensive A beta plaques, and cerebellum, a non-vulnerable region with no A beta containing plaques. There was a marked increase in simple gangliosides GM2 and GM3 only within the cortex of all mice expressing APP(SL).

The immunosuppressant rapamycin exacerbates neurotoxicity of Abeta peptide.

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system characterized by two major lesions: extracellular senile plaques and intraneuronal neurofibrillary tangles. beta-Amyloid (Abeta) is known to play a major role in the pathogenesis of AD. Protein synthesis and especially translation initiation are modulated by different factors, including the PKR/eIF2 and the mTOR/p70S6K pathways.

Activated mTOR and PKR kinases in lymphocytes correlate with memory and cognitive decline in Alzheimer's disease.

Background: The control of translation, involving the kinases mTOR (mammalian target of rapamycin) and PKR (double-stranded RNA-dependent protein kinase), modulates cell survival and death and is altered in the brains of patients with Alzheimer's disease (AD). In AD increased susceptibility of lymphocytes to apoptosis has been reported.

Methods: We investigated the level of the kinases mTOR and PKR and the eukaryotic initiation factor 2alpha (eIF2alpha) in lymphocytes of patients with AD in comparison with controls.