Acquired temperature-sensitive paralysis as a biomarker of declining neuronal function in aging Drosophila
Abstract
General locomotor activity decreases with normal aging in animals and could be partially explained by decreases in neuronal function. Voltage-gated Na(+) channels are essential in initiating and propagating rapid electrical impulses underlying normal locomotor activity and behavior in animals. Isolation of mutations conferring temperature-sensitive (ts) paralysis has been an extremely powerful paradigm for identifying genes involved in neuronal functions, such as membrane excitability and synaptic transmission. For instance, decreased expression of wild-type Na(+) channels in flies harboring the no-action-potential (nap) mutant allele (mle(napts)) confers rapid and reversible ts paralysis, because of failure of action potential propagation. Here, we report that aging wild-type Drosophila gradually develops an acquired susceptibility to ts paralysis that is indistinguishable from that seen in young ts paralytic mle(napts) mutants. Moreover, we show that this general age-dependent susceptibility is also present in mle(napts) flies, although the effects are shifted to lower temperature regimes. The mle(napts) flies also exhibit decreased lifespan and increased frailty. Paralysis and decreased lifespan of mle(napts) flies were part...Continue Reading
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