Interleukin-17A Mediates Hippocampal Damage and Aberrant Neurogenesis Contributing to Epilepsy-Associated Anxiety

In-Young Choi; Mi-La Cho; Kyung-Ok Cho

doi:10.3389/fnmol.2022.917598

Interleukin-17A Mediates Hippocampal Damage and Aberrant Neurogenesis Contributing to Epilepsy-Associated Anxiety

Front Mol Neurosci. 2022 Jul 6:15:917598. doi: 10.3389/fnmol.2022.917598. eCollection 2022.

Authors

In-Young Choi¹, Mi-La Cho^{2

3}, Kyung-Ok Cho^{1

3

4

5}

Affiliations

¹ Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
² Department of Medical Life Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
³ Department of Biomedicine and Health Sciences, The Catholic University of Korea, Seoul, South Korea.
⁴ Catholic Neuroscience Institute, The Catholic University of Korea, Seoul, South Korea.
⁵ Institute for Aging and Metabolic Diseases, The Catholic University of Korea, Seoul, South Korea.

Abstract

Anxiety disorder is one of the most common comorbidities in temporal lobe epilepsy (TLE), but its neurobiological mechanisms remain unclear. Here we identified a novel target, interleukin-17A (IL-17A), which can contribute to TLE-associated anxiety. Epileptic seizures were induced in 6-week-old IL-17A wild-type (WT) and knockout (KO) mice by pilocarpine injection. To evaluate anxiety level, we subjected mice to open field and elevated plus maze (EPM) tests and measured the time animals spent in center zone or open arms. Epileptic IL-17A WT mice showed thigmotaxis and reluctance to stay in open arms, whereas IL-17A KO mice spent more time in the center area and open arms, suggesting alleviated anxiety in epilepsy. Histological assessments revealed that hippocampal neuronal death as evaluated by Fluoro-Jade B staining was significantly reduced in IL-17A KO mice. Moreover, at 6 weeks after pilocarpine-induced status epilepticus, the number of hilar ectopic granule cells was also markedly decreased by IL-17A deficiency without a difference in the proliferation of neural progenitors or the generation of newborn neurons in the dentate gyrus. Taken together, our data demonstrated that IL-17A deletion mitigates TLE-associated anxiety behavior, possibly via the hippocampal neuroprotection and the reduction of seizure-induced aberrant neurogenesis.

Keywords: IL-17A; aberrant neurogenesis; anxiety; epilepsy; hippocampus; neuronal death; seizures.