Kalirin Reduction Rescues Psychosis-Associated Behavioral Deficits in APPswe/PSEN1dE9 Transgenic Mice

Publication date: Available online 16 February 2017
Source:Neurobiology of Aging
Author(s): J.M. Krivinko, S.L. Erickson, E.E. Abrahamson, Z.P. Wills, M.D. Ikonomovic, P. Penzes, R.A. Sweet
Psychosis in Alzheimer disease (AD+P) represents a distinct clinical and neurobiological AD phenotype, and is associated with more rapid cognitive decline, higher rates of abnormal behaviors, and increased caregiver burden compared to AD without psychosis. On a molecular level, AD+P is associated with greater reductions in the protein kalirin, a guanine exchange factor which has also been linked to the psychotic disease, schizophrenia. In this study, we sought to determine the molecular and behavioral consequences of kalirin reduction in APPswe/PSEN1dE9 mice. We evaluated mice with and without kalirin reduction during tasks measuring psychosis-associated behaviors and spatial memory. We found that kalirin reduction in APPswe/PSEN1dE9 mice significantly attenuated psychosis-associated behavior at 12 months of age without changing spatial memory performance. The 12 month old APPswe/PSEN1dE9 mice with reduced kalirin levels also had increased levels of the active, phosphorylated form of p21 protein (Cdc42/Rac)-activated kinases (PAKs), which function in signaling pathways for maintenance of dendritic spine density, morphology, and function.



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