Talampanel reduces the level of motoneuronal calcium in transgenic mutant SOD1 mice only if applied presymptomatically

Abstract

We tested the efficacy of treatment with talampanel in a mutant SOD1 mouse model of ALS by measuring intracellular calcium levels and loss of spinal motor neurons. We intended to mimic the clinical study; hence, treatment was started when the clinical symptoms were already present. The data were compared with the results of similar treatment started at a presymptomatic stage. Transgenic and wild-type mice were treated either with talampanel or with vehicle, starting in presymptomatic or symptomatic stages. The density of motor neurons was determined by the physical disector, and their intracellular calcium level was assayed electron microscopically. Results showed that motor neurons in the SOD1 mice exhibited an elevated calcium level, which could be reduced, but not restored, with talampanel only when the treatment was started presymptomatically. Treatment in either presymptomatic or symptomatic stages failed to rescue the motor neurons. We conclude that talampanel reduces motoneuronal calcium in a mouse model of ALS, but its efficacy declines as the disease progresses, suggesting that medication initiation in the earlier stages of the disease might be more effective.

Key words::

• Talampanel
• AMPA receptor
• mSOD1 model
• intracellular calcium
• motor neuron

Acknowledgements

This study was supported by OTKA and the Hungarian Office for Research and Technology (GVOP-3.2.1. 2004-04-0052/3.0, TÁMOP-4.2.2/08/1/2008-0002 and TéT IT27/2007). We thank Teva Pharmaceutical Industries LTD (Petah Tiqva, Israel) for kindly providing the talampanel.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.