IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0083050.html
   My bibliography  Save this article

Maintenance of Basal Levels of Autophagy in Huntington’s Disease Mouse Models Displaying Metabolic Dysfunction

Author

Listed:
  • Barbara Baldo
  • Rana Soylu
  • Åsa Petersén

Abstract

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hypothalamus might be involved in the metabolic dysfunction. Several mouse models of HD that display metabolic dysfunction have hypothalamic pathology, and expression of mutant huntingtin in the hypothalamus has been causally linked to the development of metabolic dysfunction in mice. Although the pathogenic mechanisms by which mutant huntingtin exerts its toxic functions in the HD brain are not fully known, several studies have implicated a role for the lysososomal degradation pathway of autophagy. Interestingly, changes in autophagy in the hypothalamus have been associated with the development of metabolic dysfunction in wild-type mice. We hypothesized that expression of mutant huntingtin might lead to changes in the autophagy pathway in the hypothalamus in mice with metabolic dysfunction. We therefore investigated whether there were changes in basal levels of autophagy in a mouse model expressing a fragment of 853 amino acids of mutant huntingtin selectively in the hypothalamus using a recombinant adeno-associate viral vector approach as well as in the transgenic BACHD mice. We performed qRT-PCR and Western blot to investigate the mRNA and protein expression levels of selected autophagy markers. Our results show that basal levels of autophagy are maintained in the hypothalamus despite the presence of metabolic dysfunction in both mouse models. Furthermore, although there were no major changes in autophagy in the striatum and cortex of BACHD mice, we detected modest, but significant differences in levels of some markers in mice at 12 months of age. Taken together, our results indicate that overexpression of mutant huntingtin in mice do not significantly perturb basal levels of autophagy.

Suggested Citation

  • Barbara Baldo & Rana Soylu & Åsa Petersén, 2013. "Maintenance of Basal Levels of Autophagy in Huntington’s Disease Mouse Models Displaying Metabolic Dysfunction," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-15, December.
  • Handle: RePEc:plo:pone00:0083050
    DOI: 10.1371/journal.pone.0083050
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083050
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0083050&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0083050?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Noboru Mizushima & Beth Levine & Ana Maria Cuervo & Daniel J. Klionsky, 2008. "Autophagy fights disease through cellular self-digestion," Nature, Nature, vol. 451(7182), pages 1069-1075, February.
    2. Taichi Hara & Kenji Nakamura & Makoto Matsui & Akitsugu Yamamoto & Yohko Nakahara & Rika Suzuki-Migishima & Minesuke Yokoyama & Kenji Mishima & Ichiro Saito & Hideyuki Okano & Noboru Mizushima, 2006. "Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice," Nature, Nature, vol. 441(7095), pages 885-889, June.
    3. Masaaki Komatsu & Satoshi Waguri & Tomoki Chiba & Shigeo Murata & Jun-ichi Iwata & Isei Tanida & Takashi Ueno & Masato Koike & Yasuo Uchiyama & Eiki Kominami & Keiji Tanaka, 2006. "Loss of autophagy in the central nervous system causes neurodegeneration in mice," Nature, Nature, vol. 441(7095), pages 880-884, June.
    4. Yoshinobu Ichimura & Takayoshi Kirisako & Toshifumi Takao & Yoshinori Satomi & Yasutsugu Shimonishi & Naotada Ishihara & Noboru Mizushima & Isei Tanida & Eiki Kominami & Mariko Ohsumi & Takeshi Noda &, 2000. "A ubiquitin-like system mediates protein lipidation," Nature, Nature, vol. 408(6811), pages 488-492, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiaoting Zhou & You-Kyung Lee & Xianting Li & Henry Kim & Carlos Sanchez-Priego & Xian Han & Haiyan Tan & Suiping Zhou & Yingxue Fu & Kerry Purtell & Qian Wang & Gay R. Holstein & Beisha Tang & Junmin, 2024. "Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Alexandra K. Davies & Julian E. Alecu & Marvin Ziegler & Catherine G. Vasilopoulou & Fabrizio Merciai & Hellen Jumo & Wardiya Afshar-Saber & Mustafa Sahin & Darius Ebrahimi-Fakhari & Georg H. H. Borne, 2022. "AP-4-mediated axonal transport controls endocannabinoid production in neurons," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Amy-Jayne Hutchings & Bita Hambrecht & Alexander Veh & Neha Jadhav Giridhar & Abdolhossein Zare & Christina Angerer & Thorben Ohnesorge & Maren Schenke & Bhuvaneish T. Selvaraj & Siddharthan Chandran , 2024. "Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Catherine J. Greene & Jenny A. Nguyen & Samuel M. Cheung & Corey R. Arnold & Dale R. Balce & Ya Ting Wang & Adrian Soderholm & Neil McKenna & Devin Aggarwal & Rhiannon I. Campden & Benjamin W. Ewanchu, 2022. "Macrophages disseminate pathogen associated molecular patterns through the direct extracellular release of the soluble content of their phagolysosomes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Afshin Saffari & Barbara Brechmann & Cedric Böger & Wardiya Afshar Saber & Hellen Jumo & Dosh Whye & Delaney Wood & Lara Wahlster & Julian E. Alecu & Marvin Ziegler & Marlene Scheffold & Kellen Winden, 2024. "High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    6. Jongchan Woo & Seungmee Jung & Seongbeom Kim & Yurong Li & Hyunjung Chung & Tatiana V. Roubtsova & Honghong Zhang & Celine Caseys & Dan Kliebenstein & Kyung-Nam Kim & Richard M. Bostock & Yong-Hwan Le, 2024. "Attenuation of phytofungal pathogenicity of Ascomycota by autophagy modulators," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Yoshito Minami & Atsushi Hoshino & Yusuke Higuchi & Masahide Hamaguchi & Yusaku Kaneko & Yuhei Kirita & Shunta Taminishi & Toshiyuki Nishiji & Akiyuki Taruno & Michiaki Fukui & Zoltan Arany & Satoaki , 2023. "Liver lipophagy ameliorates nonalcoholic steatohepatitis through extracellular lipid secretion," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Kuninori Suzuki & Shingo Nakamura & Mayumi Morimoto & Kiyonaga Fujii & Nobuo N Noda & Fuyuhiko Inagaki & Yoshinori Ohsumi, 2014. "Proteomic Profiling of Autophagosome Cargo in Saccharomyces cerevisiae," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-9, March.
    9. Ao Bian & Mingjun Shi & Brianna Flores & Nancy Gillings & Peng Li & Shirley Xiao Yan & Beth Levine & Changying Xing & Ming Chang Hu, 2017. "Downregulation of autophagy is associated with severe ischemia-reperfusion-induced acute kidney injury in overexpressing C-reactive protein mice," PLOS ONE, Public Library of Science, vol. 12(9), pages 1-21, September.
    10. M. O. Aremu & Hashim Ibrahim, 2017. "Dietary Phospholipids and Phytostrerols: A Review on Some Nigerian Vegetable Oils," International Journal of Sciences, Office ijSciences, vol. 6(09), pages 94-102, September.
    11. Kai-Chih Hung & Hui-Ju Huang & Ming-Wei Lin & Yen-Ping Lei & Anya Maan-yuh Lin, 2014. "Roles of Autophagy in MPP+-Induced Neurotoxicity In Vivo: The Involvement of Mitochondria and α-Synuclein Aggregation," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-9, March.
    12. Yuki Takakura & Moeka Machida & Natsumi Terada & Yuka Katsumi & Seika Kawamura & Kenta Horie & Maki Miyauchi & Tatsuya Ishikawa & Nobuko Akiyama & Takao Seki & Takahisa Miyao & Mio Hayama & Rin Endo &, 2024. "Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    13. Athina Varveri & Miranta Papadopoulou & Zacharias Papadovasilakis & Ewoud B. Compeer & Aigli-Ioanna Legaki & Anastasios Delis & Vasileia Damaskou & Louis Boon & Sevasti Papadogiorgaki & Martina Samiot, 2024. "Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    14. Hayden Weng Siong Tan & Guang Lu & Han Dong & Yik-Lam Cho & Auginia Natalia & Liming Wang & Charlene Chan & Dennis Kappei & Reshma Taneja & Shuo-Chien Ling & Huilin Shao & Shih-Yin Tsai & Wen-Xing Din, 2022. "A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0083050. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.