Abstract
Recent studies show that alcohol exposure can induce glial production of neuroimmune factors in the CNS. Of these, IL-6 has gained attention because it is involved in a number of important physiological and pathophysiological processes that could be affected by alcohol-induced CNS production of IL-6, particularly under conditions of excessive alcohol use. For example, IL-6 has been shown to play a role in hippocampal behaviors and synaptic plasticity (long-term potentiation; LTP) associated with memory and learning. Surprisingly, in our in vitro studies of LTP at the Schaffer collateral to CA1 pyramidal neuron synapse in hippocampus from transgenic mice that express elevated levels of astrocyte produced IL-6 (TG), LTP was not altered by the increased levels of IL-6. However, exposure to acute alcohol revealed neuroadaptive changes that served to protect LTP against the alcohol-induced reduction of LTP observed in hippocampus from non-transgenic control mice (WT). Here we examined the induction phase of LTP to assess if presynaptic neuroadaptive changes occurred in the hippocampus of TG mice that contributed to the resistance of LTP to alcohol. Results are consistent with a role for IL-6-induced neuroadaptive effects on presynaptic mechanisms involved in transmitter release in the resistance of LTP to alcohol in hippocampus from the TG mice. These actions are important with respect to a role for IL-6 in physiological and pathophysiological processes in the CNS and in CNS actions of alcohol, especially when excessive alcohol used is comorbid with conditions associated with elevated levels of IL-6 in the CNS.
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Acknowledgements
We thank Alana C. Puro, Jessica C. Manos, and Kenneth C. Reyes for performing some of the experiments.
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This work was supported by National Institutes of Health Grants AA024484 and the Integrated Neuroscience Initiative on Alcoholism (INIA)-West Grant AA020893, and The Scripps Research Institute’s Mouse Behavioral Assessment Core.
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DLG and AJR conceived of the project and designed the experiments. DLG analyzed and interpreted the data with support from RH. RH carried out the experiments. All authors contributed to manuscript preparation and approved the final version.
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Gruol, D.L., Hernandez, R.V. & Roberts, A. Alcohol Enhances Responses to High Frequency Stimulation in Hippocampus from Transgenic Mice with Increased Astrocyte Expression of IL-6. Cell Mol Neurobiol 41, 1299–1310 (2021). https://doi.org/10.1007/s10571-020-00902-6
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DOI: https://doi.org/10.1007/s10571-020-00902-6