Abstract
Activation of microglial cells (brain macrophages) soon after status epilepticus has been suggested to be critical for the pathogenesis of mesial temporal lobe epilepsy (MTLE). However, microglial activation in the chronic phase of experimental MTLE has been scarcely addressed. In this study, we questioned whether microglial activation persists in the hippocampus of pilocarpine-treated, epileptic Wistar rats and to which extent it is associated with segmental neurodegeneration. Microglial cells were immunostained for the universal microglial marker, ionized calcium-binding adapter molecule-1 and the activation marker, CD11b (also known as OX42, Mac-1). Using quantitative morphology, i.e., stereology and Neurolucida-based reconstructions, we investigated morphological correlates of microglial activation such as cell number, ramification, somatic size and shape. We find that microglial cells in epileptic rats feature widespread, activation-related morphological changes such as increase in cell number density, massive up-regulation of CD11b and de-ramification. The parameters show heterogeneity in different hippocampal subregions. For instance, de-ramification is most prominent in the outer molecular layer of the dentate gyrus, whereas CD11b expression dominates in hilus. Interestingly, microglial activation only partially correlates with segmental neurodegeneration. Major neuronal death in the hilus, CA3 and CA1 coincides with strong up-regulation of CD11b. However, microglial activation is also observed in subregions that do not feature neurodegeneration, such as the molecular and granular layer of the dentate gyrus. This in vivo study provides solid experimental evidence that microglial cells feature widespread heterogeneous activation that only partially correlates with hippocampal segmental neuronal loss in experimental MTLE.
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Notes
Also known as the α-subunit of the complement receptor 3, macrophage antigen-1, integrin αMβ2 and OX42.
Abbreviations
- AHS:
-
Ammon’s horn sclerosis
- CA1:
-
Cornu ammonis subregion 1
- CA3:
-
Cornu ammonis subregion 3
- CR3:
-
Complement receptor 3
- DGgr:
-
Dentate gyrus granular layer
- DGmi:
-
Dentate gyrus inner molecular layer
- DGmo:
-
Dentate gyrus outer molecular layer
- Hil:
-
Hilus
- Hipp:
-
Hippocampal formation
- Iba-1:
-
Ionized calcium-binding adapter molecule-1
- MTLE:
-
Mesial temporal lobe epilepsy
- Epi:
-
Chronic epileptic rats
- Sub:
-
Subiculum
- Sham-subpop:
-
Microglial subpopulation in sham rats
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This work was supported by the Deutsche Forschungsgemeinschaft (SFB-TR3).
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IP, AL, UH and OK declare no conflict of interest. AF performed her experimental part during her Master’s studentship in (2). AF’s current position in Chiesi Hellas does not interfere with the current work and declares free of any financial interest.
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Papageorgiou, I.E., Fetani, A.F., Lewen, A. et al. Widespread activation of microglial cells in the hippocampus of chronic epileptic rats correlates only partially with neurodegeneration. Brain Struct Funct 220, 2423–2439 (2015). https://doi.org/10.1007/s00429-014-0802-0
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DOI: https://doi.org/10.1007/s00429-014-0802-0