Abstract
Lipopolysaccharide (LPS), a fragment of the bacterial cell wall, specifically interacting with protein complexes on the cell surface, can induce the production of pro-inflammatory and apoptotic signaling molecules, leading to the damage and death of brain cells. Similar effects have been noted in stroke and traumatic brain injury, when the leading factor of death is glutamate (Glu) excitotoxicity too. But being an amphiphilic molecule with a significant hydrophobic moiety and a large hydrophilic region, LPS can also non-specifically bind to the plasma membrane, altering its properties. In the present work, we studied the effect of LPS from Escherichia coli alone and in combination with the hyperstimulation of Glu-receptors on the functional state of mitochondria and Ca2+ homeostasis, oxygen consumption and the cell survival in primary cultures from the rats brain cerebellum and cortex. In both types of cultures, LPS (0.1–10 μg/ml) did not change the intracellular free Ca2+ concentration ([Ca2+]i) in resting neurons but slowed down the median of the decrease in [Ca2+]i on 14% and recovery of the mitochondrial potential (ΔΨm) after Glu removal. LPS did not affect the basal oxygen consumption rate (OCR) of cortical neurons; however, it did decrease the acute OCR during Glu and LPS coapplication. Evaluation of the cell culture survival using vital dyes and the MTT assay showed that LPS (10 μg/ml) and Glu (33 μM) reduced jointly and separately the proportion of live cortical neurons, but there was no synergism or additive action. LPS-effects was dependent on the type of culture, that may be related to both the properties of neurons and the different ratio between neurons and glial cells in cultures. The rapid manifestation of these effects may be the consequence of the direct effect of LPS on the rheological properties of the cell membrane.
Highlights
A blood-brain barrier damaged by trauma, stroke, or disease does not represent a reliable barrier to infection (Dando et al, 2014; Brown and Ginsberg, 2019)
Cultures of cortical neurons were less resistant to the toxic Glu administration, and cortical cultures had a greater proportion of neurons with delayed calcium deregulation (DCD), despite a lower Glu concentration (Supplementary Figure 2A)
In the present work, employing primary neuronal cultures, we studied whether the bacterial endotoxin LPS can enhance the neurotoxic effect of glutamate, without induction of an inflammatory response
Summary
A blood-brain barrier damaged by trauma, stroke, or disease does not represent a reliable barrier to infection (Dando et al, 2014; Brown and Ginsberg, 2019). The death of neurons and glial cells can have long-term effects, even after antibiotics eliminate the bacteria that caused the infection. Bacterial infection can induce the apoptosis of neuronal stem cells, impairing the formation of new neurons in the brain (Hofer et al, 2011). The bacterial toxin-induced apoptosis of cells of the immune system may have a partly positive effect, preventing the excessive elimination of brain cells by the body’s own immune system (Djukic et al, 2014; Pardon, 2015). In order to develop effective methods for preventing the death of brain cells, it is necessary to understand the mechanisms leading to cell death during bacterial infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
