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.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Chee FC,Mudher A,Cuttle MF,Newman TA,MacKay D,Lovestone S,Shepherd Ddoi
10.1016/j.nbd.2005.05.029keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
918-28issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(05)00162-2journal_volume
20pub_type
杂志文章abstract：:Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of glycine and γ-aminobutyric acid type-A receptors (GABAARs) at inhibitory synapses. An impairment of GABAergic synaptic inhibition represents a key pathway of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene have...
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journal_title：Neurobiology of disease
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journal_title：Neurobiology of disease
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更新日期：2005-03-01 00:00:00
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journal_title：Neurobiology of disease
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journal_title：Neurobiology of disease
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journal_title：Neurobiology of disease
pub_type： 杂志文章
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abstract：:Heterozygous in frame duplications of the PHOX2B gene, leading to polyalanine (polyAla) expansions ranging from +5 to +13 residues of a 20-alanine stretch, have been identified in the vast majority of patients affected with Congenital Central Hypoventilation Syndrome (CCHS), a rare neurocristopathy characterized by ab...
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