PP2A is protein phosphatase-2A. Inhibition of PP2A (by PP2A inhibitors 1 and 2) results in hyperphosphorylation and accumulation of tau protein. Hyperphosphorylated tau is a major component of neurofibrillary tangles – a pathological hallmark of Alzheimer’s Disease (AD). Hence PP2A inhibition represents a putative new approach for a rodent model of AD. The goal of this study was to evaluate the effects of PP2A inhibition on dendritic branching in cortical pyramids in rats that wereinjected ICV with an adeno- associated virus for expression of: (1) Inhibitor 1 full length (I1 FL) (2) Inhibitor 2 full length (I2 FL) (3) Inhibitor 2 amino terminal fragment (I2 NTF) (4) GFP (Green Fluorescent Protein), Control Rat brains were subsequently Golgi stained and from coded slides randomly selected layer V pyramids were evaluated for the amount and distribution of their basilar dendritic arbor using Sholl analysis. Results showed that administration of both I2 groups (full length and amino terminal fragment) resulted in more dendritic branching than either the GFP control or the I1 full length inhibitor. Tau hyperphosphoryation by PP2A-inhibition did not result in a diminution of cortical branching. Additional studies are ongoing to further characterize the validity of this model.
Scholar Commons Citation
Verma, Sean; Iqbal, Khalid; and Mervis, Ronald F., "Dendritic Alterations in a Tauopathy Rat Model of Alzheimer’s Disease Using PP2A Inhibition" (2011). Outstanding Honors Theses. 69.