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.

Effects of chronic scopolamine treatment on cognitive impairment and neurofilament expression in the mouse hippocampus

“…In our preliminary study, we found that there were no significant differences in protein levels of NFs in the hippocampus between 3 and 4 weeks SCO-treated groups. For reference, we recently reported that significant difference in the protein level of myelin basic protein, which is most abundant structural protein in the myelin, was not found in the hippocampus between 3 and 4 weeks SCO-treated groups ( 4 ).…”

“…The animals used in the passive avoidance test were used for spatial learning and memory test using the Morris water maze task according to our published protocol ( 4 ). In short, a circular pool (90 cm in diameter and 45 cm height) filled with water was conceptually divided into four quadrants, and a platform (6 cm in diameter and 29 cm in height) was placed in one quadrant 1 cm below the water surface.…”

Vanillin and 4-hydroxybenzyl alcohol attenuate cognitive impairment and the reduction of cell proliferation and neuroblast differentiation in the dentate gyrus in a mouse model of scopolamine-induced amnesia

“…SCO was administered by intraperitoneal injection once daily for 4 weeks, and vanillin or 4-HBA were administered orally using a feeding needle once daily for 4 weeks. Experimental dosage of SCO, vanillin, and 4-HBA was selected on the basis of previous studies [2022]. …”

“…Spatial learning and memory test was performed using the Morris water maze test according to a published procedure by Park et al [22]. In short, a circular pool (90 cm in diameter and 45 cm height) filled with water was conceptually divided into four quadrants, and a platform (6 cm in diameter and 29 cm in height) was placed in one quadrant 1 cm below the water surface.…”

“…As previously described [22], in short, mice were anesthetized with sodium pentobarbital (30 mg/kg) and fixed with 4% paraformaldehyde. Their brains were removed and serially sectioned into 30-µm coronal sections in a cryostat (Leica, Wetzlar, Germany).…”