title: Sensorimotor Cortex Injection of Adeno-Associated Viral Vector Mediates Knockout of PTEN in Neurons of the Brain and Spinal Cord of Mice.
abstract: Cre/loxP-mediated inactivation of phosphatase and tensin homolog (PTEN) is proposed to be a promising therapeutic agent for promoting CNS and PNS regeneration. And adeno-associated virus (AAV) vector has been developed as an attractive gene delivery system with proven safety. In the present study, we investigated Cre/loxP-mediated knockout of PTEN in the sensorimotor cortex, hippocampus, and spinal cord in PTEN floxed mice by immunohistological analysis of PI3K/AKT/mTOR expression in neurons of the sensorimotor cortex, hippocampus, and spinal cord after sensorimotor cortex injection of AAV-Cre. Two weeks after injection of AAV-Cre, the sensorimotor cortex, hippocampus, and spinal cord were dissected and examined the expression of downstream molecules pAKT and pS6 of PI3K/AKT signaling pathway. The results showed that remote delivery of AAV-Cre through sensorimotor cortex injection mediated PTEN knockout in neurons of the sensorimotor cortex, hippocampus, and spinal cord. We propose sensorimotor cortex injection of AAV may provide a potential strategy of gene therapy for the CNS diseases.
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, People's Republic of China. cp_yang_1999@yahoo.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Cadet Brigade, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Cadet Brigade, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Cadet Brigade, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Cadet Brigade, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D055786:Gene Knockout Techniques / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007276:Injections, Intraventricular; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D066191:Sensorimotor Cortex / Q000166:cytology / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Adeno-associated virus (AAV); Axonal transport; Gene therapy; Hippocampus; Sensorimotor cortex; Spinal cord