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Fig. 5 | Molecular Neurodegeneration

Fig. 5

From: Tau mutant A152T, a risk factor for FTD/PSP, induces neuronal dysfunction and reduced lifespan independently of aggregation in a C. elegans Tauopathy model

Fig. 5

Mutant TauAT worms show presynaptic protein mislocalization in dendrites of PVD neurons and neurotransmission defects. a Schematic representation of a PVD neuron with normal localization of mCherry::RAB-3 (pre-synaptic marker, red dots) and a PVD neuron with altered localization. The branched morphology represents the dendritic compartment; the unbranched ventral process is the axon. b Representative images of dendrites and axons at day 1 and day 3 of the mentioned transgenes. In non-tg and Tauwt worms (-lo and -hi), mCherry::RAB-3 localizes in the axonal compartment and is excluded from the dendrites in young adults (day 1). By contrast, TauAT-lo worms show mCherry::RAB-3 mislocalized to the dendrites (yellow arrowheads) and a reduced distribution in the axons. With age, Tauwt (-lo and -hi) also show slight mislocalization to the dendritic compartments (yellow arrowheads). Yellow dotted areas correspond to the dendrite not visible in non-tg, Tauwt-lo and Tauwt-hi worms at day1. c Quantification of the fractions of animals with mislocalized presynaptic mCherry::RAB-3 puncta in tau-transgenes at day 1 (d1) and day 3 (d3). Non-tg worms serve as control. Error bars denote mean ± SEM, n ≥ 20. **P ≤ 0.01, ***P ≤ 0.001. Paired t-test with unequal variance was used for comparison. d Time-dependent paralysis induced by aldicarb (acetylcholine esterase inhibitor). Data represents the percentage of worms (mean ± SEM) still able to move on 1 mM aldicarb plates after being touched, as a function of time. Non-tg and Tauwt-lo worms are highly sensitive (bottom curves, grey and olive). Tauwt-hi, TauAT-lo and TauAT-hi worms show some resistance (blue, ochre, green curves, resp.). Strongly resistant lev-1 (AChR mutant carrying the e211 allele) and mildly resistant rab-3 (Ras GTPase mutant carrying the js49 allele) are used as additional controls (black and red curve, resp). After applying two-way ANOVA with Bonferroni correction, P < 0.01 at time points 45 and 180 min, whereas P < 0.001 at time points 90 and 135 min is obtained for Tauwt-hi, TauAT-lo and TauAT-hi against non-tg. n = 20 animals, three independent repetitions. e Time-dependent paralysis induced by levamisole (acetylcholine receptor agonist). Data represents the percentage of worms (mean ± SEM) still able to move on 0.2 mM levamisole plates after being touched, as a function of time. All the four tau-lines were as sensitive to levamisole as non-tg. Strongly resistant lev-1 (e211) is shown as an additional control. n = 20 animals, three independent repetitions

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