Reduced mitochondrial size in hippocampus and psychiatric behavioral changes in the mutant mice with homologous mutation of
DDP1
MTFP1
TIMM8A
deafness-dystonia-optic neuronopathy (DDON) syndrome
mitochondrial fission
Journal
Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935
Informations de publication
Date de publication:
2022
2022
Historique:
received:
21
06
2022
accepted:
01
08
2022
entrez:
12
9
2022
pubmed:
13
9
2022
medline:
13
9
2022
Statut:
epublish
Résumé
Deafness-dystonia-optic neuronopathy (DDON) syndrome, a condition that predominantly affects males, is caused by mutations in Histological analysis, transmission electron microscopy (EM), Western blotting, hearing measurement by auditory brainstem response (ABR), and behavioral observation were compared between the MUT mice and wild-type (WT) littermates. The weight of the female MUT mice was less than that of the WT mice. Among MUT mice, both male and female mice showed hearing impairment, anxiety-like behavior by the elevated plus maze test, and cognitive deficit by the Morris water maze test. Furthermore, the female MUT mice exhibited coordination problems in the balance beam test. Although the general neuronal loss was not found in the hippocampus of the MUT genotype, EM assessment indicated that the mitochondrial size showing as aspect ratio and form factor in the hippocampus of the MUT strain was significantly reduced compared to that in the WT genotype. More importantly, this phenomenon was correlated with the upregulation of translation of mitochondrial fission process protein 1(Mtfp1)/mitochondrial 18 kDa protein (Mtp18), a key fission factor that is a positive regulator of mitochondrial fission and mitochondrial size. Interestingly, significant reductions in the size of the uterus and ovaries were noted in the female MUT mice, which contributed to significantly lower fertility in the MUT mice. Together, a homologous mutation in the
Sections du résumé
Background
UNASSIGNED
Deafness-dystonia-optic neuronopathy (DDON) syndrome, a condition that predominantly affects males, is caused by mutations in
Materials and methods
UNASSIGNED
Histological analysis, transmission electron microscopy (EM), Western blotting, hearing measurement by auditory brainstem response (ABR), and behavioral observation were compared between the MUT mice and wild-type (WT) littermates.
Results
UNASSIGNED
The weight of the female MUT mice was less than that of the WT mice. Among MUT mice, both male and female mice showed hearing impairment, anxiety-like behavior by the elevated plus maze test, and cognitive deficit by the Morris water maze test. Furthermore, the female MUT mice exhibited coordination problems in the balance beam test. Although the general neuronal loss was not found in the hippocampus of the MUT genotype, EM assessment indicated that the mitochondrial size showing as aspect ratio and form factor in the hippocampus of the MUT strain was significantly reduced compared to that in the WT genotype. More importantly, this phenomenon was correlated with the upregulation of translation of mitochondrial fission process protein 1(Mtfp1)/mitochondrial 18 kDa protein (Mtp18), a key fission factor that is a positive regulator of mitochondrial fission and mitochondrial size. Interestingly, significant reductions in the size of the uterus and ovaries were noted in the female MUT mice, which contributed to significantly lower fertility in the MUT mice.
Conclusion
UNASSIGNED
Together, a homologous mutation in the
Identifiants
pubmed: 36090790
doi: 10.3389/fncel.2022.972964
pmc: PMC9453755
doi:
Types de publication
Journal Article
Langues
eng
Pagination
972964Informations de copyright
Copyright © 2022 Ouattara, Chen, Huang, Chen, Song, Xiao, Li, Guan, Li, Jiang, Xu, Pan and Hu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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