Author(s): Li XM, Su F, Ji MH, Zhang GF, Qiu LL,
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Abstract BACKGROUND: A prolonged isoflurane exposure may lead to cognitive decline in rodents. Neuregulin 1 (NRG1)-ErbB4 signaling plays a key role in the modulation of hippocampal synaptic plasticity through regulating the neurotransmission. The authors hypothesized that hippocampal NRG1-ErbB4 signaling is involved in isoflurane-induced cognitive impairments in aged mice. METHODS: Fourteen-month-old C57BL/6 mice were randomized to receive 100\% O2 exposure, vehicle injection after 100\% O2 exposure, vehicle injection after exposure to isoflurane carried by 100\% O2, NRG1-β1 injection after exposure to isoflurane carried by 100\% O2, and NRG1-β1 and an ErbB4 inhibitor AG1478 injection after exposure to isoflurane carried by 100\% O2. Fear conditioning test was used to assess the cognitive function of mice 48-h postexposure. The brain tissues were harvested 48-h postexposure to determine the levels of NRG1, ErbB4, p-ErbB4, parvalbumin, and glutamic acid decarboxylase 67 in the hippocampus using Western blotting, enzyme-linked immunosorbent assay, and immunofluorescence. RESULTS: The percentage of freezing time to context was decreased from 50.28 ± 11.53\% to 30.82 ± 10.00\%, and the hippocampal levels of NRG1, p-ErbB4/ErbB4, parvalbumin, and glutamic acid decarboxylase 67 were decreased from 172.79 ± 20.85 ng/g, 69.15 ± 12.20\%, 101.68 ± 11.21\%, and 104.71 ± 6.85\% to 112.92 ± 16.65 ng/g, 42.26 ± 9.71\%, 75.89 ± 10.26\%, and 73.87 ± 16.89\%, respectively, after isoflurane exposure. NRG1-β1 attenuated the isoflurane-induced hippocampus-dependent cognitive impairment and the declines in the hippocampal NRG1, p-ErbB4/ErbB4, parvalbumin, and glutamic acid decarboxylase 67. AG1478 inhibited the rescuing effects of NRG1-β1. CONCLUSION: Disruption of NRG1-ErbB4 signaling in the parvalbumin-positive interneurons might, at least partially, contribute to the isoflurane-induced hippocampus-dependent cognitive impairment after exposure to isoflurane carried by 100\% O2 in aged mice.
This article was published in Anesthesiology
and referenced in Journal of Addiction Research & Therapy