Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice

Peng Hao Hai, Katsumi Doh-Ura, Hiroshi Nakanishi

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Abstract

Cathepsin S (CS) is a lysosomal/endosomal cysteine protease especially expressed in cells of a mononuclear lineage including microglia. To better understand the role of CS in microglia, we investigated microglial responses after a facial nerve axotomy in CS-deficient (CS-/-) and wild-type mice. Microglia in both groups accumulated in the facial motor nucleus following axotomy. However, the mean number of microglia in CS-/-mice on the axotomized side was significantly smaller than that in wild-type mice. Microglia were found to adhere to injured motoneurons in wild-type mice, whereas microglia abutted on injured motoneurons without spreading on their surface in CS-/- mice. At the same time, the axotomy-induced down-regulation of tenasin-R, an antiadhesive perineuronal net for microglia, was partially abrogated in CS-/- mice. Primary cultured microglia prepared from CS-/- mice showed that CS deficiency caused significant suppression of migration and transmigration of microglia. In CS-/- mice, impaired recruitments of circulating monocytes and T lymphocytes and reduced expression of the class II major compatibility complex on the axotomized side were observed. Interestingly, cathepsin B, a typical lysosomal cysteine protease, was markedly expressed on the axotomized side in CS-/- but not in wild-type microglia. Finally, we compared axotomy-induced neuronal death in the two groups and found that the percentage of motoneurons that survived in CS-/- mice was significantly smaller than that in wildtype mice. The present study strongly suggests that CS plays a role in the migration and activation of microglia to protect facial motoneurons against axotomy-induced injury.

Original languageEnglish
Pages (from-to)2196-2206
Number of pages11
JournalJournal of Neuroscience Research
Volume85
Issue number10
DOIs
Publication statusPublished - Aug 1 2007

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cathepsin S
Axotomy
Facial Nerve
Microglia
Motor Neurons
Cysteine Proteases

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice. / Hai, Peng Hao; Doh-Ura, Katsumi; Nakanishi, Hiroshi.

In: Journal of Neuroscience Research, Vol. 85, No. 10, 01.08.2007, p. 2196-2206.

Research output: Contribution to journalArticle

Hai, Peng Hao ; Doh-Ura, Katsumi ; Nakanishi, Hiroshi. / Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice. In: Journal of Neuroscience Research. 2007 ; Vol. 85, No. 10. pp. 2196-2206.
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