TY  - JOUR
AB  - Significant progress has been made with regard to understanding how the adult brain responds after a stroke. However, a large number of patients continue to suffer lifelong disabilities without adequate treatment. In the present study, we have analyzed possible microanatomical alterations in the contralesional hippocampus from the ischemic stroke mouse model tMCAo 12-14 weeks after transient middle cerebral artery occlusion. After individually injecting Lucifer yellow into pyramidal neurons from the CA1 field of the hippocampus, we performed a detailed three-dimensional analysis of the neuronal complexity, dendritic spine density, and morphology. We found that, in both apical (stratum radiatum) and basal (stratum oriens) arbors, CA1 pyramidal neurons in the contralesional hippocampus of tMCAo mice have a significantly higher neuronal complexity, as well as reduced spine density and alterations in spine volume and spine length. Our results show that when the ipsilateral hippocampus is dramatically damaged, the contralesional hippocampus exhibits several statistically significant selective alterations. However, these alterations are not as significant as expected, which may help to explain the recovery of hippocampal function after stroke. Further anatomical and physiological studies are necessary to better understand the modifications in the "intact" contralesional lesioned brain regions, which are probably fundamental to recover functions after stroke.
AU  - Merino-Serrais, P.*
AU  - Plaza-Alonso, S.*
AU  - Hellal, F.
AU  - Valero-Freitag, S.*
AU  - Kastanauskaite, A.*
AU  - Plesnila, N.*
AU  - DeFelipe, J.*
C1  - 68901
C2  - 53752
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Structural changes of CA1 pyramidal neurons after stroke in the contralesional hippocampus.
JO  - Brain Pathol.
PB  - Wiley
PY  - 2023
SN  - 1015-6305
ER  - 

TY  - JOUR
AB  - Mitochondrial translation defects are a continuously growing group of disorders showing a large variety of clinical symptoms including a wide range of neurological abnormalities. To date, mutations in PTCD3, encoding a component of the mitochondrial ribosome, have only been reported in a single individual with clinical evidence of Leigh syndrome. Here, we describe three additional PTCD3 individuals from two unrelated families, broadening the genetic and phenotypic spectrum of this disorder, and provide definitive evidence that PTCD3 deficiency is associated with Leigh syndrome. The patients presented in the first months of life with psychomotor delay, respiratory insufficiency and feeding difficulties. The neurologic phenotype included dystonia, optic atrophy, nystagmus and tonic-clonic seizures. Brain MRI showed optic nerve atrophy and thalamic changes, consistent with Leigh syndrome. WES and RNA-seq identified compound heterozygous variants in PTCD3 in both families: c.[1453-1G>C];[1918C>G] and c.[710del];[902C>T]. The functional consequences of the identified variants were determined by a comprehensive characterization of the mitochondrial function. PTCD3 protein levels were significantly reduced in patient fibroblasts and, consistent with a mitochondrial translation defect, a severe reduction in the steady state levels of complexes I and IV subunits was detected. Accordingly, the activity of these complexes was also low, and high-resolution respirometry showed a significant decrease in the mitochondrial respiratory capacity. Functional complementation studies demonstrated the pathogenic effect of the identified variants since the expression of wild-type PTCD3 in immortalized fibroblasts restored the steady-state levels of complexes I and IV subunits as well as the mitochondrial respiratory capacity. Additionally, minigene assays demonstrated that three of the identified variants were pathogenic by altering PTCD3 mRNA processing. The fourth variant was a frameshift leading to a truncated protein. In summary, we provide evidence of PTCD3 involvement in human disease confirming that PTCD3 deficiency is definitively associated with Leigh syndrome.
AU  - Muñoz-Pujol, G.*
AU  - Ortigoza-Escobar, J.D.*
AU  - Paredes-Fuentes, A.J.*
AU  - Jou, C.*
AU  - Ugarteburu, O.*
AU  - Gort, L.*
AU  - Yubero, D.*
AU  - García-Cazorla, A.*
AU  - O'Callaghan, M.*
AU  - Campistol, J.M.*
AU  - Muchart, J.*
AU  - Yépez, V.A.*
AU  - Gusic, M.
AU  - Gagneur, J.*
AU  - Prokisch, H.
AU  - Artuch, R.*
AU  - Ribes, A.*
AU  - Urreizti, R.*
AU  - Tort, F.*
C1  - 66846
C2  - 53318
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Leigh syndrome is the main clinical characteristic of PTCD3 deficiency.
JO  - Brain Pathol.
VL  - 33
IS  - 3
PB  - Wiley
PY  - 2022
SN  - 1015-6305
ER  -