Di-n-butyl phthalate disrupts neuron maturation in primary rat embryo neurons and male C57BL/6 mice.

Di-n-butyl phthalate (DBP) is commonly used as a plasticizer and its usage continues to increase in conjunction with plastic consumption. DBP is readily released into air, drinking water, and soil, and unfortunately, is a potent endocrine disrupter that impairs central nervous system functions. Previously DBP was found to (1) arrest the cell cycle of C17.2 neural progenitor cells (NPCs) at the G1 phase, (2) reduce numbers of newly generated neural stem cells in the mouse hippocampus, and (3) adversely affect learning and memory. Other investigators also noted DBP-mediated neurotoxic effects, but as yet, no study has addressed the adverse effects of DBP on neuronal differentiation. Data demonstrated that at 200 µM DBP induced apoptosis in rat embryo primary neurons by increasing reactive oxygen species levels and inducing mitochondrial dysfunction. However, no significant effect was detected on neurons at concentrations of ≤100 µM. In contrast, doublecortin/microtubule associated protein-2 (DCX/MAP2) immunocytochemistry showed that DBP at 100 µM delayed neuronal maturation by increasing protein levels of DCX (an immature neuronal marker), without markedly affecting cell viability. Further in vivo studies confirmed that DCX+ cell numbers were significantly elevated in the hippocampus of DBP-treated mice, indicating that DBP delayed neuronal maturation, which is known to be associated with impaired memory retention. Data demonstrated that DBP might disrupt neuronal maturation, which is correlated with reduced neurocognitive functions.

Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.

Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson's Disease Model.

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson's disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP+)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP+-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.