Upregulation of brain utrophin does not rescue behavioral alterations in dystrophin-deficient mice

摘要: Dystrophin, the protein responsible for X-linked Duchenne muscular dystrophy (DMD), is normally expressed in both muscle and brain, which explains that its loss also leads to cognitive deficits. The utrophin protein, an autosomal homolog, a natural candidate dystrophin replacement patients. Pharmacological upregulation of endogenous improves physiology dystrophin-deficient mdx mice, represents potential therapeutic tool has advantage allowing delivery various organs following peripheral injections. Whether this could alleviate deficits, however, not been explored. Here, we first investigated basal expression all utrophins dystrophins brain mice found no evidence spontaneous compensation by utrophins. Then, show systemic chronic, spaced injections arginine butyrate (AB) alterations upregulate adult mice. AB selectively upregulated Up395, while reducing Up113 Up71. This, was associated with significant improvement behavioral functions typically affected include exploration, emotional reactivity, spatial fear memories. We suggest did overcome dysfunctions because regional cellular coincide untreated nor it AB-treated While treatments based on modulation may DMD phenotypes certain tissues coexpress same cells, would likely require acting specific dystrophin-dependent mechanisms.