Evaluating of microtubules and tau in corticosterone-induced depression, similar pathological processes as in beta-amyloid peptide neurotoxicity

Abstract

OBJECTIVES: Among different risk factors, it has been implicated that depression can be a risk factor for developing Alzheimer's disease (AD). Cytoskeleton plays important role in stabilize both axonal transport and even the spines. It has been reported for the perturbation of cytoskeleton in AD and different psychiatric disorders. Therefore, we aim to evaluate cytoskeletal protein microtubules, phosphorylation of tau and actin in experimental models of depression and AD. METHODS: We have used corticosterone as a model agent for depression and oligomeric ß-amyloid (Aß) peptide as a toxin agent for AD. We employed cultured hippocampal neurons for as our experimental model. We used live-cell imaging, Western-blot analysis and immunofluorescent staining to evaluate the stability of microtubules, phosphorylation of tau and even the abundant of postsynaptic density protein PSD-95. RESULTS: After exposure to Aß or corticosterone, aggregation of microtubules was found in neurons expressing GFP-tubulin. The level of acetylated tubulin was reduced, suggesting instable microtubules. On the other hand, increased phosphorylation of tau occurred. The effect was not limited to microtubule. By expressing mCherry-actin in cultured hippocampal neurons, Aß or corticosterone also induced actin rod formation and reduction of PSD95 protein. To maintain the stability of microtubules by taxol, all the above pathological changes could be attenuated. CONCLUSION: Our results have proved that corticosterone in depression induces similar pathological changes of microtubules and actin as if Aß in AD, which may explain why depression can be a risk factor for promoting cognitive impairment in AD.