Nebulization of low-dose aspirin ameliorates Huntington’s pathology in N171-82Q transgenic mice

Abstract

Huntington Disease (HD), a devastating hereditary neurodegenerative disorder, is caused by expanded CAG trinucleotide repeats in the huntingtin gene (Htt) on chromosome 4. Currently, there is no effective therapy for HD. Although aspirin, acetylsalicylic acid, is one of the most widely-used analgesics throughout the world, it has some side effects. Even at low doses, oral aspirin can cause gastrointestinal symptoms, such as heartburn, upset stomach, or pain. Therefore, to bypass the direct exposure of aspirin to stomach, here, we described a new mode of use of aspirin and demonstrated that nebulization of low-dose of aspirin (10 μg/mouse/d=0.4 mg/kg body wt/d roughly equivalent to 28 mg/adult human/d) alleviated HD pathology in N171-82Q transgenic mice. Our immunohistochemical and western blot studies showed that daily aspirin nebulization significantly reduced glial activation, inflammation and huntingtin pathology in striatum and cortex of N171-82Q mice. Aspirin nebulization also protected transgenic mice from brain volume shrinkage and improved general motor behaviors. Collectively, these results highlight that nebulization of low-dose aspirin may have therapeutic potential in the treatment of HD.