Loss of MBNL1-mediated retrograde BDNF signaling in the myotonic dystrophy brain.

ABSTRACT: Reduced brain volume including atrophy in grey and white matter is commonly seen in myotonic dystrophy type 1 (DM1). DM1 is caused by an expansion of CTG trinucleotide repeats in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene. Mutant DMPK mRNA containing expanded CUG RNA (DMPK-CUG^exp) sequesters cytoplasmic MBNL1, resulting in morphological impairment. How DMPK-CUG^exp and loss of MBNL1 cause histopathological phenotypes in the DM1 brain remains elusive. Here, we show that BDNF-TrkB retrograde transport is impaired in neurons expressing DMPK-CUG^exp due to loss of cytoplasmic MBNL1 function. We reveal that mature BDNF protein levels are reduced in the brain of the DM1 mouse model EpA960/CaMKII-Cre. Exogenous BDNF treat

SUBMITTER: Wang PY 

PROVIDER: S-EPMC10018927 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature