AAV-mediated conditional deletion of PTEN in the adult sensorimotor cortex causes robust hypertrophy of cortical motoneurons

Society for Neuroscience Chicago 2015

Poster 310. Spinal Cord Injury: Animal Models and Human Studies Location: Hall A Time: Monday, October 19, 2015, 8:00 AM – 12:00 PM Program#/Poster#: 310.16/H15
Topic: C.10. Trauma
Support: NIH Grant 5T32GM008620 NIH Grant NS047718 Generous private donations

Title: AAV-mediated conditional deletion of PTEN in the adult sensorimotor cortex causes robust hypertrophy of cortical motoneurons


Abstract: Previous studies have reported neuronal hypertrophy and cortical enlargement following deletion of the phosphatase and tensin homolog on chromosome 10 gene (PTEN) in developing mice and in newborn neurons in adult mice. Here, we show that deletion of PTEN in adult sensorimotor triggers remarkable enlargement of individual cortical motoneurons which give rise to the corticospinal tract (CST) as well as alterations in cortical lamination. Using the same approach we have previously used to promote axon regeneration and functional recovery following spinal cord injury, AAV-Cre was injected locally into the sensorimotor cortex of adult (8 week old) mice with a lox-P flanked exon 5 of the PTEN gene. Control animals received intracortical injections of AAV-GFP. Mice were allowed to survive for up to one year following AAV injections. One group of mice with focal PTEN deletion received bilateral fluorogold injections at cervical level 5 of the spinal cord one week prior to perfusion to retrogradely label the cells of origin of the CST. Brain sections were immunostained for PTEN to identify the region of PTEN deletion and for phosphorylated ribosomal protein S6 (pS6), which is a marker for mTOR activation. In sections immunostained for PTEN, the area of deletion was marked by a complete absence of immunostaining in a region about 1mm in diameter. Immunostaining for pS6 revealed intensely stained neuronal cell bodies and processes within the region of PTEN deletion; pS6-positive pyramidal neurons in layer V were obviously larger than PTEN-positive neurons in other areas of the cortex. Neurons in layer V that were retrogradely labeled following fluorogold injections into the spinal cord were substantially larger in the area of PTEN deletion than in neighboring layer V neurons with intact PTEN expression. Our results indicate that deleting PTEN re-initiates the ability for robust neuronal growth that is normally restricted to the developmental state. These findings suggest the potential usefulness of PTEN interference in adults to protect and repair vulnerable neurons from the effects of aging traumatic injury, or neurodegenerative disease.

Disclosures: E.A. Gutilla: None. O. Steward: None.

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