Effect of Aging on the Behavior and Brain Expression of Genes Encoding Kaiso, BDNF, CREB, and STEP Proteins in Mice

Abstract

Molecular genetic factors, including DNA methylation, play a significant role in the regulation of brain aging. Methyl-CpG DNA-binding Kaiso protein is a bimodal repressor of transcription. However, its involvement in the aging process has not been previously studied. Brain-derived neurotrophic factor (BDNF), transcription factor CREB, and striatal-enriched protein tyrosine phosphatase STEP are also important indicators of age-related and pathological changes in the brain. In this work, we studied the behavior in the open field, tail suspension, and Morris water maze tests, as well as the mRNA levels of the genes encoding the Kaiso (Zbtb 33), BDNF (Bdnf), CREB (Creb), and STEP (Ptpn5) proteins in the prefrontal cortex and hippocampus in females of C57Bl/6J mouse strain at the age 6, 12, and 18 months. We found no effect of age dynamics on the locomotor activity and anxiety in the open-field test as well as on depressive-like behavior in the tail-suspension test. At the same time, a learning dysfunction was found in the Morris water-maze test in female mice at the age of 18 months. A decrease in the Bdnf gene mRNA level in the prefrontal cortex and an increase in the expression of the Creb and Ptpn5 genes in the hippocampus of female mice with age were demonstrated. No significant changes in the Zbtb33 gene expression level were found in these age groups in the studied brain structures.