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Published on: March 23, 2011
PRKCD Orchestrates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats by Regulating PINK1/PRKN Mitophagy Pathway
Yang Yu1, Wei Zhang1, Yingying Zhao1
1Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Journal of Cellular and Molecular Medicine
|August 11, 2026
Summary
Protein kinase C delta (PRKCD) exacerbates post-operative cognitive dysfunction (POCD) by disrupting mitophagy. Inhibiting PRKCD improves neuronal function and cognitive performance in sevoflurane-exposed models.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Post-operative cognitive dysfunction (POCD) is a decline in cognitive function after surgery.
- Mitophagy, the clearance of damaged mitochondria, is a key mechanism in POCD.
- Protein kinase C delta (PRKCD) is involved in mitochondrial regulation and the PINK1/PRKN mitophagy pathway.
Purpose of the Study:
- To investigate the role of PRKCD in sevoflurane (SEV)-induced POCD.
- To elucidate the mechanism of PRKCD in regulating the PINK1/PRKN mitophagy pathway in POCD.
Main Methods:
- In vitro studies using neurons and in vivo studies using aged rats exposed to sevoflurane.
- Techniques included immunofluorescence, qPCR, CCK-8 assays, mitochondrial assessments, Seahorse analysis, co-immunoprecipitation, western blotting, and behavioral tests.
- PRKCD expression was manipulated (interference and overexpression) to assess its effects.
Main Results:
- Sevoflurane upregulated PRKCD expression in neurons and aged rats.
- PRKCD inhibition restored neuronal viability, mitochondrial function (MMP, OCR, MitoSOX), and normalized mitophagy markers (LC3, p62).
- PRKCD interacted with PINK1 and PRKN, influencing their expression and impacting mitochondrial damage; PRKCD knockdown improved behavioral and pathological outcomes in vivo.
Conclusions:
- PRKCD plays a crucial role in enhancing sevoflurane-induced POCD.
- PRKCD regulates the PINK1/PRKN mitophagy pathway, contributing to mitochondrial dysfunction and cognitive decline.
- Targeting PRKCD may offer a therapeutic strategy for preventing or treating POCD.

