Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-82339-5
Keywords
-
Categories
Funding
- European Regional Development Fund through the Regional Operational Program Center 2020
- Competitiveness Factors Operational Program (COMPETE 2020)
- National Funds through Foundation for Science and Technology (FCT) [UID/NEU/04539/2020, CENTRO-01-0145-FEDER-000008, CENTRO-01-0145-FEDER-022095, POCI-01-0145-FEDER-016719, SpreadSilencing POCI-01-0145-FEDER-029716, POCI-01-0145-FEDER-016390]
- SynSpread
- ModelPolyQ under the EU Joint Program
- European Union [643417]
- National Ataxia Foundation
- American Portuguese Biomedical Research Fund
- Richard Chin and Lily Lock Machado-Joseph Disease Research Fund
Ask authors/readers for more resources
Research suggests that intranasal administration of neuropeptide Y (NPY) can alleviate motor and balance impairments as well as cerebellar neuropathology in MJD mouse models, without affecting other physiological parameters.
Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available