Caspase Inhibition in Select Olfactory Neurons Restores Innate Attraction Behavior in Aged Drosophila
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{"title"=>"Caspase Inhibition in Select Olfactory Neurons Restores Innate Attraction Behavior in Aged Drosophila", "type"=>"journal", "authors"=>[{"first_name"=>"Takahiro", "last_name"=>"Chihara", "scopus_author_id"=>"7004833552"}, {"first_name"=>"Aki", "last_name"=>"Kitabayashi", "scopus_author_id"=>"56237841200"}, {"first_name"=>"Michie", "last_name"=>"Morimoto", "scopus_author_id"=>"56237603600"}, {"first_name"=>"Ken ichi", "last_name"=>"Takeuchi", "scopus_author_id"=>"35508322400"}, {"first_name"=>"Kaoru", "last_name"=>"Masuyama", "scopus_author_id"=>"16507199500"}, {"first_name"=>"Ayako", "last_name"=>"Tonoki", "scopus_author_id"=>"14057291800"}, {"first_name"=>"Ronald L.", "last_name"=>"Davis", "scopus_author_id"=>"7410189501"}, {"first_name"=>"Jing W.", "last_name"=>"Wang", "scopus_author_id"=>"56029031100"}, {"first_name"=>"Masayuki", "last_name"=>"Miura", "scopus_author_id"=>"7402799768"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"24967585", "issn"=>"15537404", "sgr"=>"84903451573", "pui"=>"373412632", "scopus"=>"2-s2.0-84903451573", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1004437"}, "id"=>"2896f89f-f714-3cf9-8619-3dce26073bbd", "abstract"=>"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 Drosophila. 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 Drosophila 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.", "link"=>"http://www.mendeley.com/research/caspase-inhibition-select-olfactory-neurons-restores-innate-attraction-behavior-aged-drosophila", "reader_count"=>44, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>4, "Student > Master"=>10, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>4, "Student > Master"=>10, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>25, "Neuroscience"=>8, "Psychology"=>3, "Social Sciences"=>2, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>8}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>25}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Germany"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1567661"], "description"=>"<p>(A) cPARP signal was detected in cell bodies of ORN-expressing mCD8::PARP::Venus. Representative image (the right panel is a magnified view of the region outlined in the left panel) of an antennal-segment cryosection from an aged fly (45-days-old). cPARP signal and mCD8::PARP::Venus expression are shown in magenta and green, respectively. Arrow in the right panel indicates a cPARP-positive cell body of an Or42b neuron. The complete structure of the third antennal segment was traceable by autofluorescence in the magenta channel. Scale bar: 10 µm. (B) Representative image of the TUNEL assay with cPARP staining. TUNEL, cPARP, and mCD8::PARP::Venus expression (mCD8) are shown in red, blue, and green, respectively. The arrow indicates the cell body of a Or42b neuron positive for both TUNEL and cPARP signal. Scale bar: 10 µm. (C–E) Cell body numbers for each antenna are shown. Data were tested by Kruskal-Wallis test, followed by Dunn's multiple comparison test (C, D) or by an unpaired t-test (E). *p<0.05, **p<0.01, ***p<0.001, n.s.: no significance. Statistical results against young wild-type (WT) or aged WT are shown above or below each box plot, respectively (C, D). Genotypes: (A, B) <i>Or42b-Gal4/+;UAS-mCD8::PARP::Venus/+</i>, (C, D) WT: <i>w;OrX-Gal4/+;UAS-H2B::ECFP/+</i>, p35: <i>w;OrX-Gal4/UAS-p35;UAS-H2B::ECFP/+</i>, p35X2: <i>w;OrX-Gal4/UAS-p35;UAS-H2B::ECFP/UAS-p35</i>, Dronc-DN: <i>w;OrX-Gal4/+;UAS-H2B::ECFP/UAS-Dronc-DN</i>, miRHG: <i>w</i>;<i>OrX-Gal4/UAS-miRHG;UAS-H2B::ECFP/+</i>, X = <i>42b</i> (C), <i>92a</i> (D). (E) <i>w;Or85a-Gal4/+;UAS-H2B::ECFP/+</i>.</p>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "or42b", "or92a", "neurons", "apoptotic"], "article_id"=>1084934, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437.g005", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selected_Or42b_and_Or92a_neurons_die_in_an_age_dependent_apoptotic_manner_/1084934", "title"=>"Selected Or42b and Or92a neurons die in an age-dependent, apoptotic manner.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 02:57:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1567641"], "description"=>"<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>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "devdase", "activation", "al", "eb", "structures", "aged"], "article_id"=>1084916, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stereotyped_DEVDase_activation_in_the_AL_and_EB_structures_of_aged_Drosophila_brains_/1084916", "title"=>"Stereotyped DEVDase activation in the AL and EB structures of aged <i>Drosophila</i> brains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 02:57:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1567657"], "description"=>"<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>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "activated", "subset", "orns", "age-dependent"], "article_id"=>1084930, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437.g004", "stats"=>{"downloads"=>1, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEVDase_is_activated_in_a_subset_of_ORNs_in_an_age_dependent_manner_/1084930", "title"=>"DEVDase is activated in a subset of ORNs in an age-dependent manner.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 02:57:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1567671"], "description"=>"<p>(A) Performance index of flies bearing the <i>Or42b-Gal4</i>, <i>Or92a-Gal4</i>, and <i>UAS-p35</i> transgenes in response to apple cider vinegar vapor in 3 or 30-day-old flies. The performance index (P.I.) to apple cider vinegar between groups was not significantly different at 3 days of age. The P.I. in <i>w(CS10)</i> was significantly lower in 30-day-old flies than in 3-day-old flies. The 30-day-old flies carrying the <i>Or42b-Gal4</i> and <i>Or92a-Gal4</i> drivers and the <i>UAS-p35</i> transgene had an enhanced P.I. compared to flies of <i>w(CS10)</i> or flies bearing only the <i>UAS-p35</i> transgene at 30 days of age. Analysis of variance (ANOVA) followed by Tukey's test was performed on P.I. values from flies of 3 or 30-day-old flies. n ≧ 7 for all groups. *p<0.05. All error bars indicate the SEM. (B–E) Two-photon imaging of PN calcium response in flies with or without expression of <i>p35</i> in Or42b neurons. GH146-positive PNs express the calcium sensor GCaMP. Response to apple cider vinegar stimulation in 2–5-day-old flies (B, C) and 45–50-day-old flies (D, E). Grayscale images show the structure of the AL. Pseudo-colored images show the response to apple cider vinegar at 0.8% SV (saturated vapor pressure) (B) and 3.2% SV (D). DM1 peak fluorescence change ΔF/F is plotted against odor concentration for 2–5-day-old flies (C) and 45–50-day-old flies (E). n = 6–10. Error bars show SEM. *p<0.05, **p<0.01 (Wilcoxon signed-rank test). Only male flies were used. All flies contain <i>GH146-LexA</i> and <i>LexAop-GCaMP1.3</i>-<i>ires</i>-<i>GCaMP1.3</i>. Flies with <i>p35</i> expression also have <i>Or42b-Gal4</i> and <i>UAS-p35</i>.</p>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "impairments", "neural", "restored", "caspase", "inhibition", "corresponding"], "article_id"=>1084944, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437.g006", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_related_impairments_of_attraction_behavior_and_neural_transmission_are_restored_by_caspase_inhibition_in_corresponding_ORNs_/1084944", "title"=>"Age-related impairments of attraction behavior and neural transmission are restored by caspase inhibition in corresponding ORNs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 02:57:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1567652"], "description"=>"<p>(A–F) mCD8::PARP::Venus was expressed by <i>elav-Gal4</i> (A: all postmitotic neurons), <i>NP1227-Gal4</i> (B: GABAergic LNs), <i>GH146-Gal4</i> (C: two-thirds of the projection neurons), and <i>pebbled-Gal4</i> (D–F: all olfactory receptor neurons [ORNs]). ORNs of brains dissected from 45-day-old but not from 1-day-old flies had cPARP signals (D, E), which were inhibited by the expression of <i>p35</i>, a caspase inhibitor (F). cPARP signals and mCD8 staining are shown in magenta and green, respectively. Scale bar: 75 µm. Genotypes: (A) <i>elav-Gal4;;UAS-mCD8::PARP::Venus</i>. (B) <i>NP1227-Gal4;UAS-mCD8::PARP::Venus</i>. (C) <i>GH146-Gal4;UAS-mCD8::PARP::Venus</i>. (D, E) <i>pebbled-Gal4;;UAS-mCD8::PARP::Venus</i>. (F) <i>pebbled-Gal4;UAS-p35/+;UAS-mCD8::PARP::Venus</i>.</p>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "activated", "orns", "aged"], "article_id"=>1084925, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437.g003", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEVDase_is_activated_in_the_ORNs_of_aged_Drosophila_brains_/1084925", "title"=>"DEVDase is activated in the ORNs of aged <i>Drosophila</i> brains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 02:57:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1567624"], "description"=>"<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>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "activation", "devdase"], "article_id"=>1084907, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spatio_temporal_activation_of_DEVDase_in_adult_Drosophila_brains_/1084907", "title"=>"Spatio-temporal activation of DEVDase in adult <i>Drosophila</i> brains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-26 02:57:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1567673"], "description"=>"<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>", "links"=>[], "tags"=>["cell biology", "Cell processes", "Cell death", "Molecular cell biology", "neuroscience", "Sensory systems", "Olfactory system", "organisms", "animals", "invertebrates", "arthropoda", "insects", "drosophila", "Drosophila melanogaster", "Model organisms", "Animal models", "caspase", "inhibition", "olfactory", "neurons", "restores", "innate", "aged"], "article_id"=>1084946, "categories"=>["Biological Sciences"], "users"=>["Takahiro Chihara", "Aki Kitabayashi", "Michie Morimoto", "Ken-ichi Takeuchi", "Kaoru Masuyama", "Ayako Tonoki", "Ronald L. Davis", "Jing W. Wang", "Masayuki Miura"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004437", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Caspase_Inhibition_in_Select_Olfactory_Neurons_Restores_Innate_Attraction_Behavior_in_Aged_Drosophila_/1084946", "title"=>"Caspase Inhibition in Select Olfactory Neurons Restores Innate Attraction Behavior in Aged <i>Drosophila</i>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-26 02:57:27"}

PMC Usage Stats | Further Information

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Relative Metric

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