DEVDase is activated in a subset of ORNs in an age-dependent manner.

<p>(A) Percentages of aged brains (45-days-old) with cPAPR signals are shown. mCD8::PARP::Venus expression by various <i>Or-Gal4</i> drivers revealed that DEVDase is activated in a subset of ORNs in an age-dependent manner. Number on each column indicates the number of brains examined. (B, C) Representative images of aged fly brains expressing mCD8::PARP::Venus by <i>Or42b-Gal4</i> (B) or <i>Or85a-Gal4</i> (C). Note that cPARP signal was frequently observed in the axons of Or42b neurons (B) while it was rare in axons of Or85a neurons (C). cPARP signal, mCD8::PARP::Venus expression, and nc82 staining are shown in magenta, green, and blue, respectively. Broken lines indicate outlines of ALs. Scale bar: 75 µm. Genotypes: (A) Or42b: <i>Or42b-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or92a: <i>Or92b-Gal4/UAS-mCD8::PARP::Venus;UAS-mCD8::PARP::Venus/+</i>. Or35a: <i>Or35a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or47b: <i>Or47b-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or22a: <i>Or22a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or85a: <i>Or85a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or67d: <i>Or67d-Gal4, yw/+;;UAS-mCD8::PARP::Venus/+</i>. Or42a: <i>Or42a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or47a: <i>Or47aGal4/+;UAS-mCD8::PARP::Venus/TM2 or TM6B</i>. Or43b: <i>Or43b-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or69a: <i>Or69a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or9a: <i>Or9a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>. Or67a: <i>Or67aGal4/+;UAS-mCD8::PARP::Venus/+</i>. Or59b: <i>Or59b-Gal4, w/+;UAS-mCD8::PARP::Venus/+;UAS-mCD8::PARP::Venus/+</i>. Or67b: <i>Or67b-Gal4/UAS-mCD8::PARP::Venus</i>. Or98a: <i>Or98aGal4/+;UAS-mCD8::PARP::Venus/+</i>. Or10a: <i>Or10a-Gal4/+;UAS-mCD8::PARP::Venus/TM2 or TM6B</i>. (B) <i>Or42b-Gal4/+;UAS-mCD8::PARP::Venus/+.</i> (C) <i>Or85a-Gal4/+;UAS-mCD8::PARP::Venus/+</i>.</p

Caspase Inhibition in Select Olfactory Neurons Restores Innate Attraction Behavior in Aged <i>Drosophila</i>

<div><p>Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of <i>Drosophila</i>. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of <i>Drosophila</i> olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.</p></div

Spatio-temporal activation of DEVDase in adult <i>Drosophila</i> brains.

<p>(A) DEVDase activity detection with mCD8::PARP::Venus. Human anti-cPARP antibodies specifically recognize the N-terminal amino acid sequences of Venus that are generated by the cleavage of mCD8::PARP::Venus. (B) Percentages of brain samples with any cPARP signal at each time point are shown. “n” indicates the number of brains examined. (C, D) cPARP signals in young fly brains (1-day-old). A brain with cPARP signal near midline and the subesophageal ganglia (SOG) (C) and only near midline, without intense signals in the SOG (D). Circles of broken lines are antennal lobes (ALs). cPARP signal and mCD8::PARP::Venus expression are shown in magenta and green, respectively. Scale bar: 50 µm. (E) Schematic drawing of a <i>Drosophila</i> adult brain. The regions outlined by broken lines are ALs and SOGs. The ellipsoid body (EB) is located on the dorsal side of the AL. OL: optic lobe. (F) Graph indicating the percentage of young brains with cPARP signals. Genotypes: (B–D, F) <i>elav-Gal4;;UAS-mCD8::PARP::Venus.</i></p

Stereotyped DEVDase activation in the AL and EB structures of aged <i>Drosophila</i> brains.

<p>(A, B, D, E) Representative aged brains (45-days-old) bearing cPARP signals (DEVDase activity) in the dorso-medial side of the AL (A), the EB structure (B), the mushroom body (MB) (D) and the local interneuron (LN) of the AL (E). mCD8::PARP::Venus was expressed in most postmitotic neurons (<i>elav-Gal4;;UAS-mCD8::PARP::Venus</i>). Circles of broken lines are ALs. cPARP signal and mCD8::PARP::Venus expression are shown in magenta and green, respectively. Scale bar: 75 µm. (C) Percentages of brains with cPAPR signal in the EB and AL at each time point are shown. “n” indicates the number of brains examined. Genotypes: (A–E) <i>elav-Gal4;;UAS-mCD8::PARP::Venus.</i></p