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Intracerebroventricular Administration of 192IgG-Saporin Alters the State of Microglia in the Neocortex

Abstract—The immunotoxin 192IgG-saporin is a powerful tool for inducing the selective death of cholinergic neurons in the basal nuclei. In this study, we investigated the effect of intracerebroventricular immunotoxin administration on the state of microglia in tissues adjacent to the ventricle (striatum and parietal cortex) and remotely located but receiving innervation from the medial septal region and diagonal band of Broca (entorhinal cortex and olfactory bulbs). Assessment of the state of glial cells was performed using immunohistochemical staining with antibodies against the microglial marker protein IBA-1 and against the astrocytic marker protein GFAP. It turned out that, in the parietal cortex, the number of microglial cells increased, however this increase was not accompanied by changes in the state of astrocytes, while in the striatum there were no changes in the state of glial cells. Analysis of the expression of the Ncf1 and Cx3Cr1 genes showed that the expression of Ncf1 increases in both the parietal and entorhinal cortex in the absence of changes in the expression of Cx3Cr1. In the striatum and olfactory bulbs, there were no changes in the expression of these genes. We also analyzed mRNA levels of the Ptprb and Slc22a8 genes expressed in blood vessels. Decreased Slc22a8 expression was observed only in the striatum, while the expression of the Ptprb gene did not change in any of the structures. The data indicate that 1.5 months after the administration of immunotoxin, microglia are activated only in the neocortical areas, not in the striatum or olfactory bulbs.

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ACKNOWLEDGMENTS

The authors are grateful to L.R. Gorbacheva (Pirogov Medical University) for technical assistance in using the Zeiss LSM700 confocal microscope.

Funding

This work was supported by the Russian Science Foundation (grant no. 16-15-10403P).

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Correspondence to A. P. Bolshakov.

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Conflict of Interest. The authors declare no conflicts of interest.

Ethical approval. All experiments were performed in accordance with the ethical principles set out in the EU Directive 2010/63/EU on animal experiments, and were approved by the Ethics Committee of Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences.

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Volobueva, M.N., Dobryakova, Y.V., Manolova, A.O. et al. Intracerebroventricular Administration of 192IgG-Saporin Alters the State of Microglia in the Neocortex. Neurochem. J. 14, 37–42 (2020). https://doi.org/10.1134/S1819712420010213

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Keywords:

  • 192IgG-saporin
  • cholinergic degeneration
  • neocortex
  • striatum
  • microglia