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Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner

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Abstract

Maintaining the cholesterol homeostasis is essential for normal CNS functioning. The enzyme responsible for elimination of cholesterol excess from the brain is cholesterol 24-hydroxylase (Cyp46). Since cholesterol homeostasis is disrupted following brain injury, in this study we examined the effect of right sensorimotor cortex suction ablation on cellular and temporal pattern of Cyp46 expression in the rat brain. Increased expression of Cyp46 at the lesion site at all post injury time points (2, 7, 14, 28 and 45 days post injury, dpi) was detected. Double immunofluorescence staining revealed colocalization of Cyp46 expression with different types of glial cells in time-dependent manner. In ED1+ microglia/macrophages Cyp46 expression was most prominent at 2 and 7 dpi, whereas Cyp46 immunoreactivity persisted in reactive astrocytes throughout all time points post-injury. However, during the first 2 weeks Cyp46 expression was enhanced in both GFAP+ and Vim+ astrocytes, while at 28 and 45 dpi its expression was mostly associated with GFAP+ cells. Pattern of neuronal Cyp46 expression remained unchanged after the lesion, i.e. Cyp46 immunostaining was detected in dendrites and cell body, but not in axons. The results of this study clearly demonstrate that in pathological conditions, like brain injury, Cyp46 displayed atypical expression, being expressed not only in neuronal cells, but also in microglia and astrocytes. Therefore, injury-induced expression of Cyp46 in microglial and astroglial cells may be involved in the post-injury removal of damaged cell membranes contributing to re-establishment of the brain cholesterol homeostasis.

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Acknowledgments

The authors thank Professor D. W. Russell for generous gift of cholesterol 24-hydroxylase antibody. This work was supported by the Ministry of Science and Technological Development, Republic of Serbia, grants 143004 (SK) and 143005 (MS).

Conflict of interest statement

No competing financial interests exist.

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Authors and Affiliations

  1. Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Blvd. Despot Stefana 142, Belgrade, Serbia

    Kosara Smiljanic, Irena Lavrnja, Aleksandra Mladenovic Djordjevic, Sabera Ruzdijic, Mirjana Stojiljkovic, Sanja Pekovic & Selma Kanazir

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  1. Kosara Smiljanic
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  2. Irena Lavrnja
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  3. Aleksandra Mladenovic Djordjevic
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  4. Sabera Ruzdijic
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  5. Mirjana Stojiljkovic
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  6. Sanja Pekovic
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  7. Selma Kanazir
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Correspondence to Selma Kanazir.

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The authors K. Smiljanic and I. Lavrnja equally contributed to this work.

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Smiljanic, K., Lavrnja, I., Mladenovic Djordjevic, A. et al. Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. Histochem Cell Biol 134, 159–169 (2010). https://doi.org/10.1007/s00418-010-0718-6

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