PV-specific loss of the transcriptional coactivator PGC-1α slows down the evolution of epileptic activity in an acute ictogenic model
| العنوان: | PV-specific loss of the transcriptional coactivator PGC-1α slows down the evolution of epileptic activity in an acute ictogenic model |
|---|---|
| المؤلفون: | Andrew J. Treveylan, Rita M. Cowell, Claudia Racca, Robert Ryley Parrish, Connie Anne Mackenzie-Gray Scott, Darren Walsh |
| المصدر: | Journal of Neurophysiology |
| بيانات النشر: | American Physiological Society, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, preictal, Interneuron, Physiology, seizure, PGC-1α, Peroxisome proliferator-activated receptor, Neocortex, SYT2, Mice, 03 medical and health sciences, 0302 clinical medicine, Interneurons, Seizures, parvalbumin, Coactivator, medicine, Animals, Latency (engineering), 030304 developmental biology, Mice, Knockout, chemistry.chemical_classification, 0303 health sciences, biology, Pyramidal Cells, General Neuroscience, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mice, Inbred C57BL, Disease Models, Animal, Parvalbumins, medicine.anatomical_structure, chemistry, Cortical Excitability, biology.protein, GABAergic, Female, Neuroscience, 030217 neurology & neurosurgery, Parvalbumin, Research Article |
| الوصف: | The transcriptional coactivator, PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), plays a key role in coordinating energy requirement within cells. Its importance is reflected in the growing number of psychiatric and neurological conditions that have been associated with reduced PGC-1α levels. In cortical networks, PGC-1α is required for the induction of parvalbumin (PV) expression in interneurons, and PGC-1α deficiency affects synchronous GABAergic release. It is unknown, however, how this affects cortical excitability. We show here that knocking down PGC-1α specifically in the PV-expressing cells (PGC-1αPV−/−) blocks the activity-dependent regulation of the synaptic proteins, SYT2 and CPLX1. More surprisingly, this cell class-specific knockout of PGC-1α appears to have a novel antiepileptic effect, as assayed in brain slices bathed in 0 Mg2+ media. The rate of occurrence of preictal discharges developed approximately equivalently in wild-type and PGC-1αPV−/− brain slices, but the intensity of these discharges was lower in PGC-1αPV−/− slices, as evident from the reduced power in the γ range and reduced firing rates in both PV interneurons and pyramidal cells during these discharges. Reflecting this reduced intensity in the preictal discharges, the PGC-1αPV−/− brain slices experienced many more discharges before transitioning into a seizure-like event. Consequently, there was a large increase in the latency to the first seizure-like event in brain slices lacking PGC-1α in PV interneurons. We conclude that knocking down PGC-1α limits the range of PV interneuron firing and this slows the pathophysiological escalation during ictogenesis. NEW & NOTEWORTHY Parvalbumin expressing interneurons are considered to play an important role in regulating cortical activity. We were surprised, therefore, to find that knocking down the transcriptional coactivator, PGC-1α, specifically in this class of interneurons appears to slow ictogenesis. This anti-ictogenic effect is associated with reduced activity in preictal discharges, but with a far longer period of these discharges before the first seizure-like events finally start. Thus, PGC-1α knockdown may promote schizophrenia while reducing epileptic tendencies. |
| تدمد: | 1522-1598 0022-3077 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae4269f0791d20236644934a328335b3Test https://doi.org/10.1152/jn.00295.2021Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ae4269f0791d20236644934a328335b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221598 00223077 |
|---|