Effects of prolonged treatment with memantine in the MRL model of CNS lupus

美金刚长期治疗对中枢神经系统狼疮 MRL 模型的影响

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作者:Katarina Marcinko, Tiffany Parsons, Jason P Lerch, John G Sled, Boris Sakic

Conclusions

Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

Methods

A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE.

Results

Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Conclusions: Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

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