Neuroinflammation and adult hippocampal neurogenesis in neuropathic pain and alkyl glycerol ethers treatment in aged mice

Tyrtyshnaia,Anna; Manzhulo,Igor; Kipryushina,Yulia; Ermolenko,Ekaterina

doi:10.3892/ijmm.2019.4142

Neuroinflammation and adult hippocampal neurogenesis in neuropathic pain and alkyl glycerol ethers treatment in aged mice

Authors:
- Anna Tyrtyshnaia
- Igor Manzhulo
- Yulia Kipryushina
- Ekaterina Ermolenko
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Affiliations: ‘A.V. Zhirmunsky National Scientific Center of Marine Biology’, Far Eastern Branch of the Russian Academy of Sciences, 690041 Vladivostok, Russia
Published online on: March 21, 2019 https://doi.org/10.3892/ijmm.2019.4142
Pages: 2153-2163
Copyright: © Tyrtyshnaia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuropathic pain is a condition characterized by unpleasant sensory and emotional experiences associated with a number of diseases or injuries affecting the sensory system through various mechanisms. In this study, we focused on the impact of chronic neuropathic pain on the microglial state and hippocampal neurogenesis in aged mice. In addition, we examined the effects of alkyl glycerol ethers (AGE) treatment on behavioral parameters, hippocampal neuronal and microglial plasticity in aged C57BL/6 mice with neuropathic pain. For the induction of neuropathic pain, we used the model of chronic constriction injury (CCI) of the sciatic nerve. We observed painful behavior in animals subjected to CCI, expressed as a decrease in locomotor activity and the development of cold allodynia. A violation of working and long‑term memory was also observed. AGE administration reduced the severity of cold allodynia and prevented memory impairment. In addition to behavioral changes, neuropathic pain was accompanied by microglial activation, changes in the hippocampal production of pro‑ and anti‑inflammatory cytokines, as well as a decrease in neurogenesis. The administration of AGE prevented the neuropathic pain‑derived effects, including M1 microglial activation and neurogenesis disruption. However, in vitro experiments demonstrated the pro‑inflammatory activation of microglial cells, emphasizing the complexity of the mechanisms underlying the pharmacological effects of AGE. On the whole, the findings of this study demonstrate that AGE treatment prevented behavioral effects of neuropathic pain in mice, and AGE may thus have potential for use in the prevention or treatment of neuropathic pain cognitive and emotional effects. However, as the mechanisms underlying this type of pain are complex, further studies are required to determine the detailed pharmacological effects of AGE.

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