Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone.
Neurogenesis from endogenous progenitor cells in the adult forebrain ventricular wall may be induced by the local viral overexpression of cognate neuronal differentiation agents, in particular BDNF. Here, we show that the overexpression of noggin, by acting to inhibit glial differentiation by subependymal progenitor cells, can potentiate adenoviral BDNF-mediated recruitment of new neurons to the adult rat neostriatum. The new neurons survive at least 2 months after their genesis in the subependymal zone and are recruited primarily as GABAergic DARPP-32+ medium spiny neurons in the caudate-putamen. The new medium spiny neurons successfully project to the globus pallidus, their usual developmental target, extending processes over several millimeters of the normal adult striatum. Thus, concurrent suppression of subependymal glial differentiation and promotion of neuronal differentiation can mobilize endogenous subependymal progenitor cells to achieve substantial neuronal addition to otherwise non-neurogenic regions of the adult brain.
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
Eva
E
Chmielnicki
Abdellatif
A
Benraiss
Aris N
AN
Economides
Steven A
SA
Goldman
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D001973:Bromodeoxyuridine; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D005917:Globus Pallidus / Q000166:cytology; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013266:Stilbamidines; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D019208:Brain-Derived Neurotrophic Factor; D001973:Bromodeoxyuridine; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D013266:Stilbamidines; D000099176:Noggin Protein; C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt