- Title
- Astrocyte Responses to Complement Peptide C3a are Highly Context-Dependent
- Creator
- Pekna, Marcela; Siqin, Sumen; de Pablo, Yolanda; Stokowska, Anna; Naluai, Åsa Torinsson; Pekny, Milos
- Relation
- Neurochemical Research Vol. 48, Issue 12 September 2022, p. 1233-1241
- Publisher Link
- http://dx.doi.org/10.1007/s11064-022-03743-5
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2022
- Description
- Astrocytes perform a range of homeostatic and regulatory tasks that are critical for normal functioning of the central nervous system. In response to an injury or disease, astrocytes undergo a pronounced transformation into a reactive state that involves changes in the expression of many genes and dramatically changes astrocyte morphology and functions. This astrocyte reactivity is highly dependent on the initiating insult and pathological context. C3a is a peptide generated by the proteolytic cleavage of the third complement component. C3a has been shown to exert neuroprotective effects, stimulate neural plasticity and promote astrocyte survival but can also contribute to synapse loss, Alzheimer’s disease type neurodegeneration and blood–brain barrier dysfunction. To test the hypothesis that C3a elicits differential effects on astrocytes depending on their reactivity state, we measured the expression of Gfap, Nes, C3ar1, C3, Ngf, Tnf and Il1b in primary mouse cortical astrocytes after chemical ischemia, after exposure to lipopolysaccharide (LPS) as well as in control naïve astrocytes. We found that C3a down-regulated the expression of Gfap, C3 and Nes in astrocytes after ischemia. Further, C3a increased the expression of Tnf and Il1b in naive astrocytes and the expression of Nes in astrocytes exposed to LPS but did not affect the expression of C3ar1 or Ngf. Jointly, these results provide the first evidence that the complement peptide C3a modulates the responses of astrocytes in a highly context-dependent manner.
- Subject
- gene expression; glia; ischemia; lipopolysaccharide; neurodegeneration
- Identifier
- http://hdl.handle.net/1959.13/1485189
- Identifier
- uon:51514
- Identifier
- ISSN:0364-3190
- Rights
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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