Developmental expression of human tau in Drosophila melanogaster glial cells induces motor deficits and disrupts maintenance of PNS axonal integrity, without affecting synapse formation

Autoři: Enrico M. Scarpelli aff001;  Van Y. Trinh aff003;  Zarrin Tashnim aff003;  Jacob L. Krans aff004;  Lani C. Keller aff001;  Kenneth J. Colodner aff003
Působiště autorů: Frank H. Netter, M.D. School of Medicine, Quinnipiac University, North Haven, CT, United States of America aff001;  Department of Biological Sciences, Quinnipiac University, Hamden, CT, United States of America aff002;  Program in Neuroscience and Behavior, Mount Holyoke College, South Hadley, MA, United States of America aff003;  Department of Neuroscience, Western New England University, Springfield, MA, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Tauopathies are a class of neurodegenerative diseases characterized by the abnormal phosphorylation and accumulation of the microtubule-associated protein, tau, in both neuronal and glial cells. Though tau pathology in glial cells is a prominent feature of many of these disorders, the pathological contribution of these lesions to tauopathy pathogenesis remains largely unknown. Moreover, while tau pathology is predominantly found in the central nervous system, a role for tau in the cells of the peripheral nervous system has been described, though not well characterized. To investigate the effects of glial tau expression on the development and maintenance of the peripheral nervous system, we utilized a Drosophila melanogaster model of tauopathy that expresses human wild-type tau in glial cells during development. We found that glial tau expression during development results in larval locomotor deficits and organismal lethality at the pupal stage, without affecting larval neuromuscular junction synapse development or post-synaptic amplitude. There was, however, a significant decrease in the decay time of synaptic potentials upon repeated stimulation of the motoneuron. Behavioral abnormalities were accompanied by glial cell death, disrupted maintenance of glial-axonal integrity, and the abnormal accumulation of the presynaptic protein, Bruchpilot, in peripheral nerve axons. Together, these data demonstrate that human tau expression in Drosophila glial cells does not affect neuromuscular junction synapse formation during development, but is deleterious to the maintenance of glial-axonal interactions in the peripheral nervous system.

Klíčová slova:

Apoptosis – Cell disruption – Central nervous system – Drosophila melanogaster – Larvae – Nerves – Phosphorylation – Synapses


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