Novel objective classification of reactive microglia following hypoglossal axotomy using hierarchical cluster analysis
- 14 September 2012
- journal article
- research article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 521 (5), 1184-1201
- https://doi.org/10.1002/cne.23228
Abstract
A total of 136 microglia were intracellularly labeled and their morphological features were evaluated by 3D morphometric measurement. According to hierarchical cluster analysis, microglia were objectively categorized into four groups termed types I–IV. The validity of this classification was confirmed by principal component analysis and linear discriminant analysis. Type I microglia were found in sham-operated mice and in mice sacrificed 28 days (D28) after axotomy. The appearance of type I cells was similar to so-called ramified microglia in a resting state. Type II microglia were mainly seen in D14 mice, which exhibited small cell bodies with thin and short processes. Interestingly, none of the already-known morphological types of microglia seemed to be comparable to type II cells. We thus named type II microglia “small ramified” cells. Types III and IV microglia were mainly seen in D3 and D7 mice and their appearances were similar to hypertrophied and bushy cells, respectively. Proliferating cell nuclear antigen (PCNA), a mitosis marker, was almost exclusively expressed in D3 mice. On the other hand, voltage-dependent potassium channels (Kv1.3/1.5), neurotoxicity-related molecules, were most highly expressed in D14 mice. Increased expression of Kv1.3/1.5 in D14 mice was suppressed by minocycline treatment. These findings indicate that type II and III microglia may be involved in neurotoxicity and mitosis, respectively. Type IV microglial cells are assumed to be in the process of losing mitotic activity and gaining neurotoxicity. Our data also suggest that type II microglia can be a potential therapeutic target against neurodegenerative diseases. J. Comp. Neurol. 521:1184–1201, 2013.This publication has 62 references indexed in Scilit:
- Involvement of Kv1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicityCell Death & Disease, 2012
- Physiology of MicrogliaPhysiological Reviews, 2011
- Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injuryJournal of Neuroinflammation, 2010
- Automated Three-Dimensional Detection and Shape Classification of Dendritic Spines from Fluorescence Microscopy ImagesPLOS ONE, 2008
- The Sholl analysis of neuronal cell images: Semi-log or log–log method?Journal of Theoretical Biology, 2007
- p38 MAPK, Microglial Signaling, and Neuropathic PainMolecular Pain, 2007
- Inter- and Intracellular Signaling in Amyotrophic Lateral Sclerosis: Role of p38 Mitogen-Activated Protein KinaseNeurodegenerative Diseases, 2005
- Inflammatory stimuli induce a new K+ outward current in cultured rat microgliaNeuroscience Letters, 1992
- Silhouettes: A graphical aid to the interpretation and validation of cluster analysisJournal of Computational and Applied Mathematics, 1987
- Hierarchical Grouping to Optimize an Objective FunctionJournal of the American Statistical Association, 1963