Ponomareva, D.; Ivanov, A.; Bregestovski, P. Analysis of the Effects of Pentose Phosphate Pathway Inhibition on the Generation of Reactive Oxygen Species and Epileptiform Activity in Hippocampal Slices. Int. J. Mol. Sci.2024, 25, 1934.
Ponomareva, D.; Ivanov, A.; Bregestovski, P. Analysis of the Effects of Pentose Phosphate Pathway Inhibition on the Generation of Reactive Oxygen Species and Epileptiform Activity in Hippocampal Slices. Int. J. Mol. Sci. 2024, 25, 1934.
Ponomareva, D.; Ivanov, A.; Bregestovski, P. Analysis of the Effects of Pentose Phosphate Pathway Inhibition on the Generation of Reactive Oxygen Species and Epileptiform Activity in Hippocampal Slices. Int. J. Mol. Sci.2024, 25, 1934.
Ponomareva, D.; Ivanov, A.; Bregestovski, P. Analysis of the Effects of Pentose Phosphate Pathway Inhibition on the Generation of Reactive Oxygen Species and Epileptiform Activity in Hippocampal Slices. Int. J. Mol. Sci. 2024, 25, 1934.
Abstract
The pentose phosphate pathway (PPP) is one of three major pathways involved in glucose metabolism, regulated by glucose-6-phosphate dehydrogenase (G6PD), controlling NADPH formation. NADPH, in turn, regulates the balance of oxidative stress and reactive oxygen species (ROS) levels. G6PD dysfunction, affecting PPP, is implicated in neurological disorders, including epilepsy. However, PPP's role in epileptogenesis and ROS production during epileptic activity remains unclear. To clarify these points, we conducted electrophysiological and imaging analyses on mouse hippocampal brain slices. Using the specific G6PD inhibitor G6PDi-1, we assessed its effects on mouse hippocampal slices, examining intracellular ROS, glucose/oxygen consumption, and ROS production during synaptic stimulation and in the 4AP epilepsy model. G6PDi-1 increased basal intracellular ROS levels and reduced synaptically induced glucose consumption but had no impact on ROS production from synaptic stimulation. In the 4AP model, G6PDi-1 didn't significantly alter spontaneous seizure frequency or H2O2 release amplitude but increased the frequency and peak amplitude of interictal events. These findings suggest that short-term PPP inhibition has a minimal impact on synaptic circuit activity.
Medicine and Pharmacology, Neuroscience and Neurology
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