Astrocytes enhance the tolerance of rat cortical neurons to glutamate excitotoxicity

Abstract

Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders, including stroke, trauma and neurodegenerative diseases. Astrocytes are the main cells for the removal of glutamate in the synaptic cleft and may affect the tolerance of neurons to the glutamate excitotoxicity. Therefore, the present study aimed to investigate the tolerance of rat cortical neurons to glutamate excitotoxicity in the presence and absence of astrocytes. Rat cortical neurons in the presence or absence of astrocytes were exposed to different concentrations of glutamate (10–2,000 µM) and 10 µM glycine for different incubation periods. After 24 h, the Cell Counting kit-8 (CCK-8) assay was used to measure the cytotoxicity to neurons in the presence or absence of astrocytes. According to the results, in the absence of astrocytes, glutamate induced a concentration-dependent decrease of neuronal survival rate compared with the control rat cortical neurons, and the neurotoxic half-maximal inhibitory concentration (IC 50 ) at 15, 30 and 60 min was 364.5, 258.5 and 138.3 µM, respectively. Furthermore, in the presence of astrocytes, glutamate induced a concentration-dependent decrease of neuronal survival rate compared with the control rat cortical neurons, and the neurotoxic IC 50 at 15, 30 and 60 min was 1,935, 932.8 and 789.3 µM, respectively. However, astrocytic toxicity was not observed when the rat cortical astrocytes alone were exposed to different concentrations of glutamate (500, 1,000 and 2,000 µM) for 6, 12 and 24 h. In conclusion, the glutamate-induced neurotoxic IC 50 values at 15, 30 and 60 min were respectively higher in the presence of astrocytes as compared with those in the absence of astrocytes, suggesting that astrocytes can protect against rat cortical neuronal acute damage induced by glutamate.

Changes of the activity of glutamine synthetase in an experimental model of hypoxic preconditioning

“…But under hypoxic conditions, when structural and functional changes and neuronal damage occur, as well as the change in the plasticity of neural networks, glial cells, retaining their ability to capture glutamate by the energy of glycolysis, cannot fully neutralize the excess glutamate due to decreased levels of glutamine synthetase. Since astroglial glutamine synthetase is an endogenous protective mechanism against glutamate neurotoxicity, the reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative diseases [15,23]. Therefore, increased expression of glutamine synthetase in astrocytes promotes the protection of neurons from the toxic effect of excess glutamate, which can be used in the search for new approaches in the treatment of neurodegenerative processes.…”

Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats

“…When neurons from the rat cortex were exposed to different concentrations of glutamate (10–2,000 µM), glutamate induced a concentration-dependent increase in neuronal death. However, astrocytes exhibited a protective function in neuronal damage induced by glutamate ( Zhang et al, 2019 ). Meanwhile, a high concentration of glutamate or activation of the ionotropic glutamate receptor AMPAR also causes oligodendrocyte precursor excitotoxicity ( Deng et al, 2006 ), inhibiting the proliferation and differentiation of OPCs ( Fannon et al, 2015 ).…”

Neuroprotective Effects of Noncanonical PAR1 Agonists on Cultured Neurons in Excitotoxicity

“…In this study, we used the widely used model of glutamate-induced neurotoxicity [21,48,49]. The exposure of cultured rat cortical neurons to glutamate (Glu, 100 µM, 40 min) led to a significant decrease in cell survival.…”