Viral Vector Reprogramming of Adult Resident Striatal Oligodendrocytes into Functional Neurons.
Mol Ther
; 25(4): 928-934, 2017 04 05.
Article
em En
| MEDLINE
| ID: mdl-28202388
ABSTRACT
Recent advances suggest that in vivo reprogramming of endogenous cell populations provides a viable alternative for neuron replacement. Astrocytes and oligodendrocyte precursor cells can be induced to transdifferentiate into neurons in the CNS, but, in these instances, reprogramming requires either transgenic mice or retroviral-mediated gene expression. We developed a microRNA (miRNA)-GFP construct that in vitro significantly reduced the expression of polypyrimidine tract-binding protein, and, subsequently, we packaged this construct in a novel oligodendrocyte preferring adeno-associated virus vector. Ten days after rat striatal transduction, the vast majority of the GFP-positive cells were oligodendrocytes, but 6 weeks to 6 months later, the majority of GFP-positive cells exhibited neuronal morphology and co-localized with the neuronal marker NeuN. Patch-clamp studies on striatal slices established that the GFP-positive cells exhibited electrophysiological properties indicative of mature neurons, such as spontaneous action potentials and spontaneous inhibitory postsynaptic currents. Also, 3 months after striatal vector administration, GFP-positive terminals in the ipsilateral globus pallidus or substantia nigra retrogradely transported fluorescent beads back to GFP-positive striatal cell bodies, indicating the presence of functional presynaptic terminals. Thus, this viral vector approach provides a potential means to harness resident oligodendrocytes as an endogenous source for in vivo neuronal replacement.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligodendroglia
/
Corpo Estriado
/
Reprogramação Celular
/
Transdiferenciação Celular
/
Vetores Genéticos
/
Neurônios
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article