Functional Impact of Corticotropin-Releasing Factor Exposure on Tau Phosphorylation and Axon Transport

• DOI: 10.1371/journal.pone.0147250
• Publication Date: 2016-01-20T20:31:01Z
• Authors: Michelle H. Le; April M. Weissmiller; Louise Monte; Po Han Lin; Tia C. Hexom; Orlangie Natera; Chengbiao Wu; Robert A. Rissman
• Keywords: Chronic Stress; Axoplasmic transport; Corticotropin-releasing hormone

Stress exposure or increased levels of corticotropin-releasing factor (CRF) induce hippocampal tau phosphorylation (tau-P) in rodent models, a process that is dependent on the type-1 CRF receptor (CRFR1). Although these preclinical studies stress-induced tau-P provide mechanistic insight for epidemiological work identifies stress as risk Alzheimer's disease (AD), actual impact neuronal function remains unclear. To determine functional consequences tau-P, we developed novel mouse cell culture system to explore acute (0.5hr) and chronic (2hr) treatment integral processes such axon transport. Consistent with vivo reports, found caused globular accumulations phosphorylated dendritic axonal processes. Furthermore, while both led significant reduction CREB activation transport brain-derived neurotrophic (BDNF), this was not case mitochondrial Acute velocity distance traveled neurons, modestly decreased greatly traveled. These results suggest cellular energetics may take priority over growth factors during stress. Tau-P required changes, co-treatment GSK kinase inhibitor prevented CRF-induced all changes. Collectively, our into peptide-induced an explanation how via lead vulnerability AD.