Effects of Chronic Scopolamine Treatment on Cognitive Impairments and Myelin Basic Protein Expression in the Mouse Hippocampus
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Myelin plays an important role in learning and memory, and degradation of myelin is a key feature in the pathogenesis of neurological disorders involving cognitive dysfunction. Myelin basic protein (MBP) is one of the most abundant structural proteins in myelin and is essential for myelin formation and compaction. In this study, we first examined changes in the distribution of MBP-immunoreactive myelinated fibers and MBP levels according to hippocampal subregion in mice following chronic systemic treatment with 1 mg/kg scopolamine (SCO) for 4 weeks. We found that SCO-induced cognitive impairments, as assayed by the water maze and passive avoidance tests, were significantly reduced 1 week after SCO treatment and the impairments were maintained without any hippocampal neuronal loss. MBP-immunoreactive myelinated fibers were easily detected in the stratum radiatum and lacunosum-moleculare of the hippocampus proper (CA1–3 region) and in the molecular and polymorphic layers of the dentate gyrus. The distribution of MBP-immunoreactive myelinated fibers was not altered 1 week after SCO treatment. However, the density of MBP-immunoreactive myelinated fibers was significantly decreased 2 weeks after SCO treatment; thereafter, the density gradually, though not significantly, decreased with time. In addition, the changing pattern of MBP levels in the hippocampus following SCO treatment corresponded to immunohistochemical changes. In brief, this study shows that chronic systemic treatment with SCO induced significant degradation of MBP in the hippocampus without neuronal loss at least 2 weeks after SCO treatment, although cognitive impairments occurred 1 week after SCO treatment.
KeywordsScopolamine Cognitive deficit Hippocampus proper Dentate gyrus Myelinated nerve fibers Myelin basic protein
The authors would like to thank Mr. Seung Uk Lee for his technical help in this study. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NO2011-0022812), and by the Bio-Synergy Research Project (NRF-2015M3A9C4076322) of the Ministry of Science, ICT and Future Planning through the National Research Foundation.
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Conflict of Interest
The authors declare that they have no potential conflicts of interest.
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