Abstract：
:CLN3 mutations cause the fatal neurodegenerative disorder, CLN3 Batten disease. The Cln3-/- mouse model displays characteristic features of the human disease including motor deficits. When mice received acidified drinking water (pH 2.5-2.9) instead of normal tap water (pH 8.4) for several generations, the motor skills of Cln3-/- mice normalized to control levels, indicating a disease-modifying effect of acidified water. Here we investigated if acidified water administered from postnatal day 21 has therapeutic benefits in Cln3-/- mice. Indeed, acidified water temporarily attenuated the motor deficits, had beneficial effects on behavioral parameters and prevented microglial activation in the brain of Cln3-/- mice. Interestingly, in control mice, acidified drinking water caused brain region-specific glial activation and significant changes in motor performance. Since the gut microbiota can influence neurological functions, we examined it in our disease model and found that the gut microbiota of Cln3-/- mice was markedly different from control mice, and acidified water differentially changed the gut microbiota composition in these mice. These results indicate that acidified water may provide therapeutic benefit to CLN3 Batten disease patients, and that the pH of drinking water is a major environmental factor that strongly influences the results of murine behavioral and pathological studies.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Johnson TB,Langin LM,Zhao J,Weimer JM,Pearce DA,Kovács ADdoi
10.1038/s41598-019-51488-zsubject
Has Abstractpub_date
2019-10-18 00:00:00pages
14962issue
1issn
2045-2322pii
10.1038/s41598-019-51488-zjournal_volume
9pub_type
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