Anti-Apoptotic and Anti-Inflammatory Role of Trans ε-Viniferin in a Neuron-Glia Co-Culture Cellular Model of Parkinson's Disease.

The polyphenol trans-ε-viniferin (viniferin) is a dimer of resveratrol, reported to hold antioxidant and anti-inflammatory properties. The aims of our study were to evaluate the neuroprotective potential of viniferin in the nerve growth factor (NGF)-differentiated PC12 cells, a dopaminergic cellular model of Parkinson's disease (PD) and assess its anti-inflammatory properties in a N9 microglia-neuronal PC12 cell co-culture system. The neuronal cells were pre-treated with viniferin, resveratrol or their mixture before the administration of 6-hydroxydopamine (6-OHDA), recognized to induce parkinsonism in rats. Furthermore, N9 microglia cells, in a co-culture system with neuronal PC12, were pre-treated with viniferin, resveratrol or their mixture to investigate whether these polyphenols could reduce lipopolysaccharide (LPS)-induced inflammation. Our results show that viniferin as well as a mixture of viniferin and resveratrol protects neuronal dopaminergic cells from 6-OHDA-induced cytotoxicity and apoptosis. Furthermore, when viniferin, resveratrol or their mixture was used to pre-treat microglia cells in our co-culture system, they reduced neuronal cytotoxicity induced by glial activation. Altogether, our data highlight a novel role for viniferin as a neuroprotective and anti-inflammatory molecule in a dopaminergic cellular model, paving the way for nutraceutical therapeutic avenues in the complementary treatments of PD.

The Neuroinflammatory and Neurotoxic Potential of Palmitic Acid Is Mitigated by Oleic Acid in Microglial Cells and Microglial-Neuronal Co-cultures.

Neuroinflammation has been implicated in the pathogenesis of neurodegeneration and is now accepted as a common molecular feature underpinning neuronal damage and death. Palmitic acid (PA) may represent one of the links between diet and neuroinflammation. The aims of this study were to assess whether PA induced toxicity in neuronal cells by modulating microglial inflammatory responses and/or by directly targeting neurons. We also determined the potential of oleic acid (OA), a monounsaturated fatty acid, to counteract inflammation and promote neuroprotection. We measured the ability of PA to induce the secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the induction of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathways, as well as the phosphorylation of c-Jun, and the expression of inducible nitric oxide synthase (iNOS). Finally, to determine whether PA exerted an indirect neurotoxic effect on neuronal cells, we employed a microglia-neuron co-culture paradigm where microglial cells communicate with neuronal cells in a paracrine fashion. Herein, we demonstrate that PA induces the activation of the NF-κB signalling pathway and c-Jun phosphorylation in N9 microglia cells, in the absence of increased cytokine secretion. Moreover, our data illustrate that PA exerts an indirect as well as a direct neurotoxic role on neuronal PC12 cells and these effects are partially prevented by OA. These results are important to establish that PA interferes with neuronal homeostasis and suggest that dietary PA, when consumed in excess, may induce neuroinflammation and possibly concurs in the development of neurodegeneration.

Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway.

Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing dopaminergic alterations in diabetes with age, the goal of this study was to characterize the state of 2 critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-term hyperglycemia, specifically the nigrostriatal motor pathway and the reward-associated mesocorticolimbic pathway. Neuronal and glial alterations were evaluated 3 and 6 months after hyperglycemia induction, demonstrating preferential degeneration of the nigrostriatal pathway complemented by a noticeable astrogliosis and loss of microglial cells throughout aging. Behavioral tests confirmed the existence of motor impairments in hyperglycemic rats that resemble early parkinsonian symptomatology in rats, pensuing from nigrostriatal alterations. These results solidify the relation between hyperglycemia and nigrostriatal dopaminergic neurodegeneration, providing new insight on the higher occurrence of Parkinson's disease in diabetic patients.