Open AccessMitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome
Author(s) -
Jing Wang,
Henning Fröhlich,
Felipe Bodaleo Torres,
Rangel L. Silva,
Gernot Poschet,
Amit Agarwal,
Gudrun Rappold
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112852119
Subject(s) - oxidative stress , cognition , cognitive impairment , oxidative phosphorylation , mitochondrion , medicine , neuroscience , psychology , bioinformatics , physical medicine and rehabilitation , biology , genetics , biochemistry
Significance FOXP1 haploinsufficiency underlies cognitive and motor impairments in individuals with FOXP1 syndrome. Here, we show that mice lacking oneFoxp1 copy exhibit similar behavioral deficits, which may be caused by striatal dysfunction. Indeed,Foxp1 +/− striatal medium spiny neurons display reduced neurite branching, and we show altered mitochondrial biogenesis and dynamics; increased mitophagy; reduced mitochondrial membrane potential, structure, and motility; and elevated oxygen species in the striatum of these animals. AsFOXP1 is highly conserved, our data strongly suggest that mitochondrial dysfunction and excessive oxidative stress contribute to the motor and cognitive impairments seen in individuals with FOXP1 syndrome. Thus, mitochondrial homeostasis is critical for normal development and can explain deficits in neurodevelopmental disorders.