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Over-expression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions

Over-expression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions
Over-expression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions
We have shown that over-expression of human tau (0N3R) in Drosophila larval motor neurons causes significant morphological and functional disruption to the neuromuscular junctions (NMJs). Tau-expressing NMJs are reduced in size with irregular and abnormal bouton structure. Immunocytochemical analysis shows that the abnormal NMJs still retain synaptotagmin expression and form active zones. Functionally, the NMJs exhibit abnormal endo/exocytosis as revealed by incorporation of the styryl dye FM1–43. Electrophysiological studies showed that with low frequency stimulation (1 Hz), evoked synaptic potentials produced from tau over-expressing motor neurons were indistinguishable from wild type, however, following high frequency stimulation (50 Hz), evoked synaptic potentials were significantly decreased. Analysis of the number and distribution of mitochondria showed that motor neurons over-expressing tau had a significant reduction in functional mitochondria in the presynaptic terminal. Collapsing the mitochondrial membrane potential in wild type larvae phenocopied the effects of tau over-expression on synaptic transmission. Our results demonstrate that tau over-expression in vivo cause a synaptic dysfunction, which may be caused by a reduced complement of functional mitochondria.
Alzheimer's disease, neurodegeneration, animal model, tau mitochondria, synapse, drosophila
0969-9961
918-928
Chee, Francis C.
8ee793d5-59cc-47bc-941a-e605de4a8191
Mudher, Amritpal
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Cuttle, Matthew F.
f0c3b2a0-9d8f-4ded-ada3-348650a60772
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
MacKay, Daniel
1b7d0644-3094-483a-a664-e2a37e80951f
Lovestone, Simon
8c74cdb9-c6cc-4f60-8ad4-beaf5b526040
Shepherd, David
11aa6858-d19c-4450-82ff-11dff9dcd9c4
Chee, Francis C.
8ee793d5-59cc-47bc-941a-e605de4a8191
Mudher, Amritpal
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Cuttle, Matthew F.
f0c3b2a0-9d8f-4ded-ada3-348650a60772
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
MacKay, Daniel
1b7d0644-3094-483a-a664-e2a37e80951f
Lovestone, Simon
8c74cdb9-c6cc-4f60-8ad4-beaf5b526040
Shepherd, David
11aa6858-d19c-4450-82ff-11dff9dcd9c4

Chee, Francis C., Mudher, Amritpal, Cuttle, Matthew F., Newman, Tracey A., MacKay, Daniel, Lovestone, Simon and Shepherd, David (2005) Over-expression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions. Neurobiology of Disease, 20 (3), 918-928. (doi:10.1016/j.nbd.2005.05.029).

Record type: Article

Abstract

We have shown that over-expression of human tau (0N3R) in Drosophila larval motor neurons causes significant morphological and functional disruption to the neuromuscular junctions (NMJs). Tau-expressing NMJs are reduced in size with irregular and abnormal bouton structure. Immunocytochemical analysis shows that the abnormal NMJs still retain synaptotagmin expression and form active zones. Functionally, the NMJs exhibit abnormal endo/exocytosis as revealed by incorporation of the styryl dye FM1–43. Electrophysiological studies showed that with low frequency stimulation (1 Hz), evoked synaptic potentials produced from tau over-expressing motor neurons were indistinguishable from wild type, however, following high frequency stimulation (50 Hz), evoked synaptic potentials were significantly decreased. Analysis of the number and distribution of mitochondria showed that motor neurons over-expressing tau had a significant reduction in functional mitochondria in the presynaptic terminal. Collapsing the mitochondrial membrane potential in wild type larvae phenocopied the effects of tau over-expression on synaptic transmission. Our results demonstrate that tau over-expression in vivo cause a synaptic dysfunction, which may be caused by a reduced complement of functional mitochondria.

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Published date: December 2005
Keywords: Alzheimer's disease, neurodegeneration, animal model, tau mitochondria, synapse, drosophila
Organisations: Biological Sciences

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Local EPrints ID: 24211
URI: https://eprints.soton.ac.uk/id/eprint/24211
ISSN: 0969-9961
PURE UUID: 9ec0a3bf-3f5e-483a-973d-47bda1b9e6b8
ORCID for Tracey A. Newman: ORCID iD orcid.org/0000-0002-3727-9258

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Date deposited: 28 Mar 2006
Last modified: 19 Feb 2019 01:37

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Contributors

Author: Francis C. Chee
Author: Amritpal Mudher
Author: Matthew F. Cuttle
Author: Daniel MacKay
Author: Simon Lovestone
Author: David Shepherd

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