Functional study of PDK1 in the cerebellum of aging mice

Acta Universitatis Medicinalis Anhui 2024 12 v.59 2065-2071     font:big middle small

Found programs: National Natural Science Foundation of China(Nos.32371053,32100811);Natural Science Research Project in Higher Education Institutions of Jiangsu Province(No.21KJB180008)

Authors:Peng Wenjie; Qi Cui; Liu Rui; Gao Jun

Keywords:aging;purkinje cells;PDK1;rpS6;PKCγ;AKT

DOI:10.19405/j.cnki.issn1000-1492.2024.12.001

〔Abstract〕 Objective To investigate the effects of 3-phosphoinositide-dependent protein kinase-1(PDK1) on the purkinje cells(PCs) in aging mice. Methods The footprint test, elevated beam-walk test and rotarod test were used to measure the gait traits, motor balance and motor coordination of mice. Immunoflourescence was used to detect the structure of the cerebellum and the morphology of cells in the cerebellum. The expression level of PDK1, protein kinase C gamma(PKCγ) and protein kinase B(also known as AKT) and the phosphorylation of ribosomal protein S6(rpS6) in the cerebellum were detected by Western blot. Results The mice showed motor defects in the overlap between forelimb and hindlimb, motor balance and motor coordination ability in an age-dependent manner. Furthermore, the cerebellum and the soma size of the PCs decreased in an age-dependent manner. However, the density of the PCs was not affected by age. Additionally, the expression level of the PDK1, PKCγ, AKT and the phosphorylation of rpS6 in the cerebellum were reduced with age. Conclusion The cerebellar size and the cell soma size of PCs decrease in the old mice. These effects may contribute to the reduction of the expression of PKCγ and AKT and the phosphorylation of rpS6 in the old mice, ultimately affecting the cerebellar motor coordination.