Changes in the prefrontal cortex after the hippocampus was injected with Aβ_25-35 via the P35/P25-CDK5-Tau...

Alzheimer's disease (AD) is one of the common neurodegenerative illnesses in aging populations around the world. Recently, psychiatric symptoms are becoming increasingly important in recognizing the manifestations of AD in addition to cognitive impairment. Some studies suggest that the prefrontal cortex (PFC) is closely related to apathy/depression, and a network may exist between the CA1 of hippocampus and PFC. However, whether the injection of Aβ₂₅₃₅ into hippocampi may result in PFC abnormalities in AD model rats is unclear. In this study, it was investigated the changes in the PFCs after the hippocampal injection via the P35/P25 - Cyclin-dependent kinase5 (CDK5) - Tau hyperphosphorylation signaling pathway. Our results demonstrated that rats injected with Aβ_25-35 showed decreased learning and memory ability, and increased depression-like behaviors compared with uninjected controls and saline-injected shams. P35/P25, CDK5, Tau[pS199], and Tau[pS202] are significantly elevated in the PFCs and hippocampi after Aβ_25-35 was injected into the hippocampi. Furthermore, P35/P25-CDK5 complexes were detected in vivo by immunofluorescence and co-immunoprecipitation. Therefore, the relative expression of proteins associated with the P35/P25-CDK5 pathway showed the same changes in the hippocampi and PFCs after Aβ_25-35 injection. These findings demonstrate a potential mechanism for prefrontal-mediated cognitive impairment and the psychiatric symptoms of AD.