Hyperactive delta isoform of PI3 kinase enables long-distance regeneration of adult rat corticospinal tract
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00604755" target="_blank" >RIV/68378041:_____/25:00604755 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10497221
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S1525001624008384?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1525001624008384?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ymthe.2024.12.040" target="_blank" >10.1016/j.ymthe.2024.12.040</a>
Alternative languages
Result language
angličtina
Original language name
Hyperactive delta isoform of PI3 kinase enables long-distance regeneration of adult rat corticospinal tract
Original language description
Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16 weeks post injury. At 12 weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16 weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Therapy
ISSN
1525-0016
e-ISSN
1525-0024
Volume of the periodical
33
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
19
Pages from-to
752-770
UT code for WoS article
001423068000001
EID of the result in the Scopus database
2-s2.0-85215387479