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

慢性东莨菪碱治疗对小鼠认知障碍及海马神经丝表达的影响

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作者:Jae-Chul Lee, Joon Ha Park, Ji Hyeon Ahn, Jinseu Park, In Hye Kim, Jeong Hwi Cho, Bich Na Shin, Tae-Kyeong Lee, Hyunjung Kim, Minah Song, Geum-Sil Cho, Dae Won Kim, Il Jun Kang, Young-Myeong Kim, Moo-Ho Won, Soo Young Choi

Abstract

Neurofilaments (NFs) including neurofilament‑200 kDa (NF‑H), neurofilament‑165 kDa (NF‑M) and neurofilament‑68 kDa (NF‑L) are major protein constituents of the brain, and serve important roles in the regulation of axonal transport. NF alteration is a key feature in the pathogenesis of neurological disorders involving cognitive dysfunction. In the present study, cognitive impairments were investigated, via assessments using the Morris water maze and passive avoidance tests, in mice following chronic systemic treatment with 1 mg/kg scopolamine (SCO) for 4 weeks. SCO‑induced cognitive impairments were significantly observed 1 week following the SCO treatment, and these cognitive deficits were maintained for 4 weeks. However, the NF immunoreactivities and levels were altered differently according to the hippocampal subregion following SCO treatment. NF‑H immunoreactivity and levels were markedly altered in all hippocampal subregions, and were significantly increased 1 week following the SCO treatment; thereafter, the immunoreactivity and levels significantly decreased with time. NF‑M immunoreactivity and levels gradually decreased in the hippocampus and were significantly decreased 4 weeks following SCO treatment. NF‑L immunoreactivity and levels gradually decreased in the hippocampus, and were significantly decreased 2 and 4 weeks following SCO treatment. In conclusion, the results of the present study demonstrated that chronic systemic treatment with SCO induced cognitive impairment from 1 week following SCO treatment, and NF expression was diversely altered according to the hippocampal subregion from 1 week following SCO treatment. These results suggest that SCO‑induced changes in NF expression may be associated with cognitive impairment.

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