Neuroprotective Effects of VGLUT1 Inhibition in HT22 Cells Overexpressing VGLUT1 Under Oxygen Glucose Deprivation Conditions.
Animals
Glucose
/ metabolism
Mice
Vesicular Glutamate Transport Protein 1
/ genetics
Membrane Potential, Mitochondrial
/ drug effects
Hippocampus
/ metabolism
Cell Hypoxia
Cell Survival
/ drug effects
Neuroprotective Agents
/ pharmacology
L-Lactate Dehydrogenase
/ metabolism
Neurons
/ metabolism
Oxygen
/ metabolism
Cell Line
Glutamic Acid
/ metabolism
Vesicular Glutamate Transport Protein 2
Brain ischemia
Chicago Sky Blue 6B
Glutamate
Oxygen glucose deprivation
Vesicular glutamate transporters
Journal
Neuromolecular medicine
ISSN: 1559-1174
Titre abrégé: Neuromolecular Med
Pays: United States
ID NLM: 101135365
Informations de publication
Date de publication:
23 Aug 2024
23 Aug 2024
Historique:
received:
28
06
2024
accepted:
20
08
2024
medline:
24
8
2024
pubmed:
24
8
2024
entrez:
23
8
2024
Statut:
epublish
Résumé
Glutamate (Glu) is a major excitatory neurotransmitter in the brain, essential for synaptic plasticity, neuronal activity, and memory formation. However, its dysregulation leads to excitotoxicity, implicated in neurodegenerative diseases and brain ischemia. Vesicular glutamate transporters (VGLUTs) regulate Glu loading into synaptic vesicles, crucial for maintaining optimal extracellular Glu levels. This study investigates the neuroprotective effects of VGLUT1 inhibition in HT22 cells overexpressing VGLUT1 under oxygen glucose deprivation (OGD) conditions. HT22 cells, a hippocampal neuron model, were transduced with lentiviral vectors to overexpress VGLUT1. Cells were subjected to OGD, with pre-incubation of Chicago Sky Blue 6B (CSB6B), an unspecific VGLUT inhibitor. Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential, and hypoxia-related protein markers (PARP1, AIF, NLRP3) were assessed. Results indicated that VGLUT1 overexpression increased vulnerability to OGD, evidenced by higher LDH release and reduced cell viability. CSB6B treatment improved cell viability and reduced LDH release in OGD conditions, particularly at 0.1 μM and 1.0 μM concentrations. Moreover, CSB6B preserved mitochondrial membrane potential and decreased levels of PARP1, AIF, and NLRP3 proteins, suggesting neuroprotective effects through mitigating excitotoxicity. This study demonstrates that VGLUT1 inhibition could be a promising therapeutic strategy for ischemic brain injury, warranting further investigation into selective VGLUT1 inhibitors.
Identifiants
pubmed: 39179680
doi: 10.1007/s12017-024-08803-3
pii: 10.1007/s12017-024-08803-3
doi:
Substances chimiques
Glucose
IY9XDZ35W2
Vesicular Glutamate Transport Protein 1
0
Neuroprotective Agents
0
L-Lactate Dehydrogenase
EC 1.1.1.27
Oxygen
S88TT14065
Slc17a7 protein, mouse
0
Slc17a6 protein, mouse
0
Glutamic Acid
3KX376GY7L
Vesicular Glutamate Transport Protein 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
35Subventions
Organisme : Narodowe Centrum Nauki
ID : 2016/21/B/NZ4/03294
Informations de copyright
© 2024. The Author(s).
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