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bioRxiv · 10.1101/2022.04.16.488241

Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia

Zhang, Y.-Q.·Chen, L.-q.·Lv, X.-j.·Guo, Q.-H.·Lv, S.-s.·Lv, N.·Jin, Y.·Xu, W.-d.
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Abstract

Patients suffering from trigeminal neuralgia (TN) are often accompanied by anxiety and depression. Whether and how microglia are involved in TN-induced anxiodepressive remains unclear. Here, we unconventionally report that TN activates ipsilateral but not contralateral hippocampal microglia, upregulates ipsilateral hippocampal ATP and interleukin1{beta} (IL-1{beta}) levels, impairs ipsilateral hippocampal long-term potentiation (LTP), and induces anxiodepressive-like behaviors in a time-dependent manner in rodents. Specifically, activation of ipsilateral hippocampal microglia is necessary for TN-induced anxiodepressive-like behaviors; and unilateral activating hippocampal microglia is sufficient to elicit an anxiodepressive state and impair LTP. Knockdown of ipsilateral hippocampal P2X7 receptor prevented TN-induced microglial activation and anxiodepressive-like behaviors. Furthermore, we demonstrate that microglia-derived IL-1{beta} mediates microglial activation-induced anxiodepressive-like behaviors and LTP impairment. Together, these findings suggest that priming of microglia with ATP/P2X7R in the ipsilateral hippocampus drives pain-related anxiodepressive-like behaviors via IL-1{beta}. Our results also reveal an asymmetric role of the bilateral hippocampus in TN-induced anxiety and depression.

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Zhang, Y.-Q., Chen, L.-q., Lv, X.-j., Guo, Q.-H., Lv, S.-s., Lv, N., Jin, Y., Xu, W.-d.. 2022-04-17. Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia. https://doi.org/10.1101/2022.04.16.488241

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