Affiliations: Center for Cellular Neurobiology and Neurodegeneration, Research Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA, USA
Correspondence:
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Corresponding author: Thomas B. Shea, PhD, Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachu-setts, Lowell, One University Avenue, Lowell, MA 01854, USA, Tel.: +1 978 9342881; Fax: +1 978-934-3044; E-mail: Thomas_Shea@uml.edu
Note: []
Communicated by Garth Hall
Abstract: Treatment of cultured neurons with ß-amyloid (Aß) evokes multiple consequences, including calcium influx, production of reactive oxygen species (ROS), hyperphosphorylation of tau. Which of these events is the major cause of Aß-induced neurodegeneration has been the subject of controversy. We undertook to determine whether or not the accumulation of hyperphosphorylated tau mediated neurodegeneration. Murine cortical neurons demonstrated increased phospho-tau immunoreactivity between 2–8 hr after treatment of murine cortical neurons with Aß25–35. Cultures underwent overall neurodegeneration between 8–16 hr as ascertained by phase-contrast microscopy, a commercial “live/dead” assay and externalization of phosphatidyl serine. Unexpectedly, however, the healthiest-appearing neurons in Aß–treated cultures contained relatively more phospho-tau immunoreactivity, while obviously degenerating neurons contained less; degenerating neurons often contained less phospho-tau immunoreactivity than did non-Aß-treated control neurons. By contrast, accumulation of reactive oxygen species, previously demonstrated to mediate Aß-induced neurodegeneration, was most prominent within visibly-degenerating neurons. These studies do not address the long-term consequences of PHF formation; however, they indicate that tau hyperphosphorylation, although a consequence of Aß treatment, does not directly contribute to acute degeneration of cultured neurons.
