Zonisamide Treatment Delays Motor Neuron Degeneration and Astrocyte Proliferation in Wobbler Mice

Abstract

Background : Zonisamide (ZNS) had multifunctional effects on several kinds of neurons. Little is known about neuroprotective effects of ZNS on motor neurons. We aimed to study whether this drug can attenuate motor neuron degeneration in wobbler mice. Methods : Wobbler mice were injected daily two doses of ZNS (0.2 mg/kg , 2.0 mg/kg , i.p.) or vehicle from aged 3 - 4 weeks at disease onset for more than 4 weeks. Motor function was evaluated by pull-strength and deformity scale of the forelimbs. Those symptomatic assessment and body weight were measured weekly. Neuropathological changes of the biceps muscle and the cervical cord were analyzed at 4 weeks posttreatment. Results : ZNS treatment (2.0 mg/kg ) significantly delayed progression of forelimb motor dysfunction compared to vehicle (P less than 0.01). Gain of body weight did not differ statistically between three groups. Higher doses of ZNS administration decreased denervation atrophy in the biceps muscle (P less than 0.01), suppressed loss of motor neurons (P less than 0.01) and inhibited astrocyte proliferation (P less than 0.01). Conclusions : The present study indicated that ZNS treatment attenuated motor neuron degeneration and astrocytosis in the wobbler mouse. This drug may have a therapeutic potential for motor neuron disease. doi:10.4021/jnr59w