Flavonoids are bioactive compounds that are known to be neuroprotective against glutamate-mediated excitotoxicity, one of the major causes of neurodegeneration. The mechanisms underlying these effects are unresolved, but recent evidence indicates flavonoids may modulate estrogen signaling, which can delay the onset and ameliorate the severity of neurodegenerative disorders. Furthermore, the roles played by glial cells in the neuroprotective effects of flavonoids are poorly understood. The aim of this study was to investigate the effects of the flavonoid agathisflavone (FAB) in primary neuron-glial co-cultures from postnatal rat cerebral cortex. Compared to controls, treatment with FAB significantly increased the number of neuronal progenitors and mature neurons, without increasing astrocytes or microglia. These pro-neuronal effects of FAB were suppressed by antagonists of estrogen receptors (ERα and ERβ). In addition, treatment with FAB significantly reduced cell death induced by glutamate and this was associated with reduced expression levels of pro-inflammatory (M1) microglial cytokines, including TNFα, IL1β and IL6, which are associated with neurotoxicity, and increased expression of IL10 and Arginase 1, which are associated with anti-inflammatory (M2) neuroprotective microglia. We also observed that FAB increased neuroprotective trophic factors, such as BDNF, NGF, NT4 and GDNF. The neuroprotective effects of FAB were also associated with increased expression of glutamate regulatory proteins in astrocytes, namely glutamine synthetase (GS) and Excitatory Amino Acid Transporter 1 (EAAT1). These findings indicate that FAB acting via estrogen signaling stimulates production of neurons in vitro and enhances the neuroprotective properties of microglia and astrocytes to significantly ameliorate glutamate-mediated neurotoxicity.
Aminochrome has been suggested as a more physiological preclinical model capable of inducing five of the six mechanisms of Parkinson's Disease (PD). Until now, there is no evidence that aminochrome induces glial activation related to neuroinflammation, an important mechanism involved in the loss of dopaminergic neurons. In this study, the potential role of aminochrome on glial activation was studied in primary mesencephalic neuron-glia cultures and microglial primary culture from Wistar rats. We demonstrated that aminochrome induced a reduction in the number of viable cells on cultures exposed to concentration between 10 and 100μM. Moreover, aminochrome induces neuronal death determined by Fluoro-jade B. Furthermore, we demonstrated that aminochrome induced reduction in the number of TH-immunoreactive neurons and reactive gliosis, featured by morphological changes in GFAP and Iba1 cells, increase in the number of OX-42 cells and increase in the number of NF-κB p50 immunoreactive cells. These results demonstrate aminochrome neuroinflammatory ability and support the hypothesis that it may be a better PD preclinical model to find new pharmacological treatment that stop the development of this disease.
The exposure to benzene is a public health problem. Although the most well-known effect of benzene is hematopoietic toxicity, there is little information about the benzene and its metabolites effects on the central nervous system (CNS). This study examined the toxic effects of 1,2-dihydroxybenzene (catechol), a benzene metabolite, to human glioblastoma GL-15 cells. GL-15 cell cultures were used as a model to provide more information about the toxic effects of aromatic compounds to the CNS. Catechol induced time- and concentration-dependent cytotoxic effects. Morphological changes, such as the retraction of the cytoplasm and chromatin clumping, were seen in cells exposed to 200 μM catechol for 48 hours. In cells exposed to 600 μM catechol for 48 hours, 78.0% of them presented condensed nuclei, and the Comet assay showed DNA damage. The percentage of cells labeled with annexin V (apoptotic cells) was greater in the group exposed to catechol (20.7%) than in control cells (0.4%). Exposure to catechol at concentrations greater than 100 μM enhanced Bax levels, and a decrease in Bcl-2 level was observed after the exposure to 600 μM catechol for 48 hours. Furthermore, catechol depleted reduced glutathione. Hence, catechol induced cell death mainly by apoptosis.
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