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.

• Klíčová slova
• CST, PI3K, axon regeneration, c-Fos, electrophysiology, pS6, signaling, skilled paw reaching, spinal cord, spinal cord injury,
• MeSH
• axony metabolismus   fyziologie   MeSH
• Dependovirus genetika   MeSH
• fosfatidylinositol-3-kinasy třídy I metabolismus   genetika   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• genetické vektory genetika   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• neurony metabolismus   MeSH
• obnova funkce MeSH
• poranění míchy * metabolismus   terapie   genetika   MeSH
• pyramidové dráhy * metabolismus   MeSH
• regenerace nervu * MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy třídy I MeSH
• fosfatidylinositol-3-kinasy MeSH