Presentation Type

Poster

Cortical Dendritic Alterations in a Rat Model of Alzheimer’s Disease Using PP2A Inhibition

Abstract

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 were injected 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.

Categories

Biomedical Sciences

Research Type

Thesis

Mentor Information

Dr. Ronald Mervis

This document is currently not available here.

Share

COinS
 

Cortical Dendritic Alterations in a Rat Model of Alzheimer’s Disease Using PP2A Inhibition

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 were injected 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.