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[State of the "protein kinase CK2-HMG14" system in age-dependent amnesia in rats]
B A Reĭkhardt1, O G Kulikova, G Iu Borisova
1Institute of Experimental Medicine, Russian Acad. Med. Sci., St. Petersburg, 197376, Acad. Pavlov St., 12, Russia.
Abstract:
It has been shown that a decrease in HMGs transcription factors phosphorylation by protein kinase CK2 may be the cause of a gene expression decline in cognitive disorders. Passive avoidance amnesia in old rats (24 month) was accompanied by a decrease in synaptosomal protein synthesis and transcription in isolated nuclei of cortex, hippocampus, and striatum. A decrease in chromatin protein kinase CK2 activity and a significant decrease in HMG14 phosphorylation by CK2 was found in old rats. CK2 selective activators, a 4-carbamoyl-5-N-methylcarbamoyl-1-ethyl-imidazole and 4,5-dicaramoyl-1-ethyl-imidazole, produced the HMG14 phosphorylation and transcription activation in old rats. At the same time, synaptosomal protein synthesis activation and passive avoidance amnesia reduction were observed in old rats. Thus, activation of CK2-HMG14 was accompanied by synaptic plasticity optimisation. The data show a high therapeutic potential of activators of CK2-HMG14.
Insights
Decreased protein kinase CK2 activity impairs gene expression and memory in aging rats. Activating CK2-HMG14 restores synaptic plasticity and reduces amnesia, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Cognitive disorders are linked to reduced gene expression, potentially caused by decreased phosphorylation of High Mobility Group (HMG) transcription factors by protein kinase CK2.
- Aging in rats is associated with impaired passive avoidance memory, decreased synaptosomal protein synthesis, and reduced transcription in brain regions like the cortex, hippocampus, and striatum.
Purpose of the Study:
- To investigate the role of protein kinase CK2 and HMG14 phosphorylation in age-related cognitive decline.
- To evaluate the therapeutic potential of CK2 activators in mitigating amnesia and restoring synaptic function in aged rats.
Main Methods:
- Assessed protein kinase CK2 activity and HMG14 phosphorylation in brain nuclei of young and aged rats.
- Administered selective CK2 activators (imidazole derivatives) to aged rats.
- Measured changes in HMG14 phosphorylation, gene transcription, synaptosomal protein synthesis, and passive avoidance memory.
Main Results:
- Aged rats exhibited decreased CK2 activity and HMG14 phosphorylation, correlating with memory deficits and reduced protein synthesis.
- CK2 activators successfully induced HMG14 phosphorylation and transcription activation in aged rats.
- Treatment with CK2 activators led to increased synaptosomal protein synthesis and significant reduction in passive avoidance amnesia.
Conclusions:
- Activation of the CK2-HMG14 pathway is crucial for maintaining synaptic plasticity and cognitive function.
- Targeting CK2-HMG14 with selective activators demonstrates significant therapeutic potential for age-related cognitive decline and amnesia.