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Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway
- Source :
- Oxidative Medicine and Cellular Longevity, Vol 2020 (2020), Oxidative Medicine and Cellular Longevity
- Publication Year :
- 2020
- Publisher :
- Hindawi Limited, 2020.
-
Abstract
- Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.
- Subjects :
- Male
0301 basic medicine
Aging
Diabetic neuropathy
Article Subject
Cell Survival
Pharmacology
PC12 Cells
Biochemistry
Neuroprotection
Diabetes Mellitus, Experimental
Lim kinase
Diglycerides
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Diabetes mellitus
Animals
Medicine
Phosphorylation
RNA, Small Interfering
Rats, Wistar
CA1 Region, Hippocampal
Protein Kinase C
Diacylglycerol kinase
Brain Diseases
Behavior, Animal
QH573-671
business.industry
Lim Kinases
Nuclear Proteins
Cell Biology
General Medicine
Cofilin
medicine.disease
Rats
Glucose
030104 developmental biology
Actin Depolymerizing Factors
RNA Interference
Signal transduction
Cytology
business
030217 neurology & neurosurgery
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 19420994 and 19420900
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....ce1f3611fca2e70bb253f54c2d9e2ad6