Distinct effect of neurotrophins delivered simultaneously by an adenoviral vector on neurite outgrowth of neural precursor cells from different regions of the brain.
For many years, it has been demonstrated that neurotrophins regulate the adult nervous system, implicating their potential as therapeutic agents for the treatment of neurodegenerative diseases. We generated adenoviral vectors encoding brain-derived neutotrophin factor (BDNF) and neurotrophin-3 (NT3) and tested either separately or together for the ability to induce differentiation of neuronal precursor cells with two different origins. Separate transduction of adenovirus delivering BDNF (BDNF-Ad) or NT3 (NT3-Ad) induced the neuronal differentiation in hippocampal and cortical precursor cells. NT3-Ad infected cells extended short neurites, whereas BDNFAd infected cells had longer neurites. In the early differentiation of hippocampal precursor cells, simultaneous infection of BDNFAd and NT3-Ad promoted further differentiation and neurite elongation compared with the separate infection of each virus. In contrast, simultaneous infection did not show the synergistic effect in the cortical precursor cells, suggesting that the neurotrophins play distinct roles in different regions of the brain. However, the numbers of neurites and spines per differentiated cells were markedly increased in cortical as well as hippocampal precursor cells, indicating the promotion of efficient neurite elongation and formation of dendritic spine, when BDNF-Ad and NT3-Ad were co-infected. These results suggest more studies in the effect of a combinatorial use of neurotrophins on different sites of brain need to be carried out to develop gene therapy protocols for neurodegenerative diseases.
Yoo
Minjoo
M
Department of Biology and Department of Life and Nanopharmaceutical Science, Research Institute of Basic Sciences, Kyunghee University, Seoul 130-701, Korea.
Joung
Insil
I
Han
Ah Mi
AM
Yoon
Hye Hyun
HH
Kwon
Yunhee Kim
YK
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D012313:RNA; D020813:Receptor, trkB