التفاصيل البيبلوغرافية
| العنوان: |
Mitochondrial Dysfunction Leads to Cortical Under-connectivity and Cognitive Impairment |
| المؤلفون: |
Fernandez, Alejandra, Meechan, Daniel W., Karpinski, Beverly A., Paronett, Elizabeth M., Bryan, Corey A., Rutz, Hanna L., Radin, Eric A., Lubin, Noah, Bonner, Erin R., Popratiloff, Anastas, Rothblat, Lawrence A., Maynard, Thomas M., LaMantia, Anthony-Samuel |
| المصدر: |
Neuron |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Article, psy, socio |
| الوصف: |
Under-connectivity between cerebral cortical association areas may underlie cognitive deficits in neurodevelopmental disorders including the 22q11.2 Deletion Syndrome (22q11DS). Using the LgDel 22q11DS mouse model, we assessed cellular, molecular and developmental origins of under-connectivity, and its consequences for cognitive function. Diminished 22q11 gene dosage reduces long-distance projections, limits axon and dendrite growth, and disrupts mitochondrial and synaptic integrity in layer 2/3 but not 5/6 projection neurons (PNs). Diminished dosage of Txnrd2, a 22q11 gene essential for reactive oxygen species catabolism in brain mitochondria, recapitulates these deficits in WT layer 2/3 PNs; Txnrd2 re-expression in LgDel layer 2/3 PNs rescues them. Anti-oxidants reverse LgDel or Txnrd2 related layer 2/3 mitochondrial, circuit and cognitive deficits. Accordingly, Txnrd2-mediated oxidative stress reduces layer 2/3 connectivity and impairs cognition in the context of 22q11 deletion. Anti-oxidant restoration of mitochondrial integrity, cortical connectivity and cognitive behavior defines oxidative stress as a therapeutic target in neurodevelopmental disorders. |
| نوع الوثيقة: |
text |
| اللغة: |
English |
| العلاقة: |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668992Test/ |
| الإتاحة: |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668992Test/ |
| حقوق: |
undefined |
| رقم الانضمام: |
edsbas.702D2AC4 |
| قاعدة البيانات: |
BASE |
