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Published on: February 27, 2018
Nebulization of low-dose aspirin ameliorates Huntington's pathology in N171-82Q transgenic mice
Susanta Mondal1,2, Shelby Prieto1, Suresh B Rangasamy1,2
1Department of Neurological Sciences, Rush University Medical Center, Chicago, USA.
Insights
Nebulized low-dose aspirin shows promise for Huntington's Disease (HD) treatment. This novel delivery method reduced key HD pathologies and improved motor function in mice, offering a potential alternative to oral aspirin.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Huntington's Disease (HD) is a hereditary neurodegenerative disorder caused by CAG trinucleotide repeats in the huntingtin gene (Htt).
- Current therapeutic options for HD are limited, and oral aspirin, while widely used, has significant gastrointestinal side effects.
- A novel delivery method is needed to explore aspirin's therapeutic potential for HD without oral side effects.
Purpose of the Study:
- To investigate the therapeutic potential of nebulized low-dose aspirin for Huntington's Disease.
- To evaluate the effects of nebulized aspirin on HD pathology and motor function in a transgenic mouse model.
Main Methods:
- Utilized N171-82Q transgenic mice, a model for Huntington's Disease.
- Administered low-dose aspirin via nebulization daily.
- Conducted immunohistochemical and Western blot analyses to assess glial activation, inflammation, and huntingtin pathology.
- Evaluated brain volume and general motor behaviors.
Main Results:
- Nebulized aspirin significantly reduced glial activation and inflammation in the striatum and cortex of HD mice.
- Huntingtin pathology was markedly decreased following daily aspirin nebulization.
- Aspirin nebulization protected against brain volume shrinkage and improved motor behaviors in the transgenic mice.
Conclusions:
- Nebulization of low-dose aspirin presents a promising therapeutic strategy for Huntington's Disease.
- This delivery method effectively mitigates key pathological hallmarks and functional deficits associated with HD.
- Further research into nebulized aspirin could lead to a new treatment paradigm for HD, bypassing oral side effects.
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.
