| Summary: | Amyloid β protein (Aβ) deposits are found in the striatum of patients with Alzheimer disease (AD) showing extrapyramidal motor dysfunction, but neuronal cell loss has not yet been detected. To clarify how Aβ impairs motor function, we analyzed intrastriatally Aβ-injected rats. Unilateral injection of Aβ(25-35) enhanced apomorphine-induced circling in an ipsilateral direction, indicating ipsilateral dysfunction of dopaminergic nigrostriatal pathways. Volumes of lesion in the Aβ(25-35)-injected striata were significantly higher than those in the saline-injected ones. The correlation between lesion volume and circling behavior was close to significance, but slightly too low, suggesting the possible involvement of other factors in the striatal dysfunction. Aβ(25-35) significantly elevated the level of thromboxane A2 (TXA2). A stable TXA2 agonist, U46619, enhanced circling behavior, and TXA2 receptor antagonists attenuated U46619- and Aβ(25-35)-enhanced circling behavior. This study demonstrated that Aβ(25-35) impairs the motor function of dopaminergic neurons via neuronal cell loss and TXA2. It also sheds light on the therapeutic potential of TXA2 receptor blockers for the neurotoxicity of Aβ.
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