Effects of Chronic Scopolamine Treatment on Cognitive Impairments and Myelin Basic Protein Expression in the Mouse Hippocampus.

Abstract

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.

• Authors: Joon Ha Park, Hyun Young Choi, Jeong-Hwi Cho, In Hye Kim, Tae-Kyeong Lee, Jae-Chul Lee, Moo-Ho Won, Bai Hui Chen, Bich-Na Shin, Ji Hyeon Ahn, Hyun-Jin Tae, Jung Hoon Choi, Jin-Young Chung, Choong-Hyun Lee, Jun Hwi Cho, Il Jun Kang, Jong-Dai Kim
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 59 Issue 4 Pg. 579-89 (Aug 2016) ISSN: 1559-1166 [Electronic] United States
• PMID: 27343058 (Publication Type: Journal Article)

Chemical References

• Muscarinic Antagonists
• Myelin Basic Protein
• Scopolamine

Topics

• Animals
• Cognitive Dysfunction (etiology, metabolism, pathology)
• Hippocampus (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred ICR
• Muscarinic Antagonists (administration & dosage, pharmacology, toxicity)
• Myelin Basic Protein (genetics, metabolism)
• Neurons (drug effects, metabolism, pathology)
• Scopolamine (administration & dosage, pharmacology, toxicity)