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Published on: March 23, 2011
Status of the "protein kinase CK2-HMG14" system in age-related amnesia in rats
B A Reikhardt1, O G Kulikova, G Yu Borisova
1Science Research Institute of Experimental Medicine, Russian Academy of Medical Sciences, 12 Academician Pavlov Street, 197376 St. Petersburg, Russia.
Abstract:
The experiments described here demonstrate that disruption of the phosphorylation of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class may be the cause of decreased gene expression in age-related cognitive deficits. Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24 months old) was accompanied by decreases in the synthesis of synaptosomal proteins and transcription in nuclei isolated from cortical, hippocampal, and striatal neurons. There was a decrease in chromatin protein kinase CK2 activity and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2. Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5-methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14 phosphorylation by protein kinase CK2, increased transcription, increased the synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged rats. Thus, activation of the "protein kinase CK2-HMG14" system is accompanied by optimization of synaptic plasticity in aged animals. The results provide evidence for the high therapeutic potential of protein kinase CK2 activators.
Insights
Disruption of protein kinase CK2-HMG14 phosphorylation contributes to cognitive decline in aging. Activating this pathway with CK2 activators improved memory and synaptic function in aged rats.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Age-related cognitive deficits are linked to decreased gene expression.
- Synaptosomal protein synthesis and neuronal transcription decline with age.
Purpose of the Study:
- To investigate the role of HMG cAMP/Ca-independent protein kinase CK2 (CK2) phosphorylation in age-related cognitive deficits.
- To explore the therapeutic potential of CK2 activators for improving cognitive function in aged animals.
Main Methods:
- Assessed conditioned passive avoidance reaction (CPAR) memory in aged rats.
- Measured synaptosomal protein synthesis and nuclear transcription rates.
- Quantified CK2 activity and HMG14 phosphorylation levels.
- Administered selective CK2 activators to aged rats.
Main Results:
- Aged rats showed impaired CPAR memory, reduced protein synthesis, and lower transcription.
- CK2 activity and HMG14 phosphorylation were significantly decreased in aged rat neurons.
- CK2 activators restored HMG14 phosphorylation, increased transcription and protein synthesis, and ameliorated memory deficits.
Conclusions:
- Disruption of the CK2-HMG14 phosphorylation pathway contributes to age-related cognitive decline.
- Activation of the CK2-HMG14 system optimizes synaptic plasticity and enhances cognitive function in aged animals.
- CK2 activators show significant therapeutic potential for treating cognitive impairments associated with aging.
