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Upregulation of Cathepsins in Olfactory Bulbs Is Associated with Transient Olfactory Dysfunction in Mice with Experimental Autoimmune Encephalomyelitis

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Abstract

Cathepsins are a family of lysosomal/endosomal proteolytic enzymes that include serine, aspartate, and cysteine proteases. The role of cathepsin in neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, remains elusive. We evaluated the expression level and localization of different cathepsins in the olfactory bulbs of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Quantitative real-time PCR results and Western blotting analyses revealed that serine, aspartate, and cysteine cathepsins are expressed at significantly higher levels in the olfactory bulbs of mice with EAE in the paralytic stage compared with those of control mice. Immunohistochemical analyses indicated that cathepsin A, D, and S were expressed in the glomerulus layer, external plexiform layer, and mitral cell layer. Furthermore, cathepsins were detected in astrocytes, microglia, inflammatory cells, and vascular cells in the olfactory bulb of EAE mice at the paralytic stage. Collectively, these results suggest that the upregulation of cathepsins in the olfactory bulb of mice with EAE is associated with transient olfactory dysfunction in autoimmune encephalomyelitis.

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Abbreviations

CNS:

Central nervous system

EAE:

Experimental autoimmune encephalomyelitis

GFAP:

Glial fibrillary acidic protein

Iba1:

Ionized calcium binding adaptor molecule 1

IB4:

Isolectin-B4

IL:

Interleukin

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

PBS:

Phosphate-buffered saline

PI:

Post-immunization

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Funding

This research was supported by the National Research Foundation of Korea (Grant number: NRF-2017R1A2B4012487 and NRF-2019R1A2C1087753).

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Authors and Affiliations

  1. Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, 102 Jejudaehakno, Jeju, 63243, Republic of Korea

    Jeongtae Kim, Meejung Ahn, Yuna Choi & Taekyun SHIN

  2. Department of Anatomy, Kosin University College of Medicine, Busan, 49267, Republic of Korea

    Jeongtae Kim

  3. Department of Animal Science, College of Life Science, Sangji University, Wonju, 26339, Republic of Korea

    Meejung Ahn

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  1. Jeongtae Kim
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  4. Taekyun SHIN
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Correspondence to Taekyun SHIN.

Ethics declarations

All experimental procedures were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals of Jeju National University (Permission No. 2017-0019 and 2019-0048). The animal protocols also conformed to current international laws and the policies of the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23, 1985, revised 1996).

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Highlights

• All tested cathepsins were upregulated in the olfactory bulb of mice with EAE.

• Cathepsins were expressed at varying levels in glial cells and inflammatory cells in the olfactory bulb of EAE mice.

• Cathepsin D potentially contributes to the clearance of cell debris in the olfactory bulb of EAE mice.

• Upregulation of cathepsins in olfactory bulbs is potentially associated with olfactory dysfunction in autoimmune encephalomyelitis.

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Kim, J., Ahn, M., Choi, Y. et al. Upregulation of Cathepsins in Olfactory Bulbs Is Associated with Transient Olfactory Dysfunction in Mice with Experimental Autoimmune Encephalomyelitis. Mol Neurobiol 57, 3412–3423 (2020). https://doi.org/10.1007/s12035-020-01952-z

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