Morphological and Dynamic Changes in Microtubules of Primary Cultured Hippocampal Neurons Stressed by β-amyloid Peptide and Corticosterone

Abstract

Objectives: To investigate the morphological and dynamic changes in microtubules in vitro models of AD and depression. Dendrite abnormality is a common pathological feature in Alzheimer's disease (AD) and depression. Dendrites elongate with protruding synapses to form communication units between neurons. They are made up of a- and ß-tubulin subunits. Microtubule-associated proteins (MAP) like MAP2 help to stabilize its structure. One of microtubule's important characteristics is its dynamicity. A group of plus end capping proteins - for example EB3 - attaches to the plus end of the microtubule and allows the microtubule to enter and exit the synapse. This movement is important to maintain synapse morphology and plasticity. Taken together, we hypothesize that pathological alterations of microtubular dynamics could contribute to disease progression in AD and depression. Methods: Primary cultures of hippocampal neurons at 14 day were exposed to different concentrations of oligomeric ß-amyloid or corticosterone for 24/48 hours. Morphology and dynamics of microtubules in neurons were investigated with fluorescent-tagged constructs of ß-tubulin and EB3, and the use of multiphoton live-cell imaging. Results: Increased concentrations of oligomeric ß-amyloid or corticosterone led to an increase in the number and size of tubulin aggregation. Co-localization between EB3 and tubulin was decreased. Conclusions: The change in tubulin morphology and its binding with EB3 may affect the normal functioning of microtubules. This in turn may contribute to dendritic regression and synaptic abnormality in AD and depression. Our results support our hypothesis and may explain why depression promotes neurodegeneration in AD.