Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain
Open accessAbstract
Neural progenitor cells persist throughout the adult forebrain subependyma, and neurons generated from them respond to brain-derived neurotrophic factor (BDNF) with enhanced maturation and survival. To induce neurogenesis from endogenous progenitors, we overexpressed BDNF in the adult ventricular zone by transducing the forebrain ependyma to constitutively express BDNF. We constructed a bicistronic adenovirus bearing BDNF under cytomegalovirus (CMV) control, and humanized green fluorescent protein (hGFP) under internal ribosomal entry site (IRES) control. This AdCMV:BDNF:IRES:hGFP (AdBDNF) was injected into the lateral ventricles of adult rats, who were treated for 18 d thereafter with the mitotic marker bromodeoxyuridine (BrdU). Three weeks after injection, BDNF averaged 1 microg/gm in the CSF of AdBDNF-injected animals but was undetectable in control CSF. In situ hybridization demonstrated BDNF and GFP mRNA expression restricted to the ventricular wall. In AdBDNF-injected rats, the olfactory bulb exhibited a >2.4-fold increase in the number of BrdU(+)-betaIII-tubulin(+) neurons, confirmed by confocal imaging, relative to AdNull (AdCMV:hGFP) controls. Importantly, AdBDNF-associated neuronal recruitment to the neostriatum was also noted, with the treatment-induced addition of BrdU(+)-NeuN(+)-betaIII-tubulin(+) neurons to the caudate putamen. Many of these cells also expressed glutamic acid decarboxylase, cabindin-D28, and DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa), markers of medium spiny neurons of the neostriatum. These newly generated neurons survived at least 5-8 weeks after viral induction. Thus, a single injection of adenoviral BDNF substantially augmented the recruitment of new neurons into both neurogenic and non-neurogenic sites in the adult rat brain. The intraventricular delivery of, and ependymal infection by, viral vectors encoding neurotrophic agents may be a feasible strategy for inducing neurogenesis from resident progenitor cells in the adult brain.
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A single injection of BDNF caused substantially more neurons to be recruited from neuronal progenitor cells.
“Even when administered a single injection of BDNF, substantially more neurons were recruited from neuronal progenitor cells (Benraiss et al., 2001).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Benraiss et al., 2001
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“For example, infusion or adenoviral delivery of BDNF into ventricles induces SVZ proliferation and neurogenesis in the striatum of rodents (Benraiss et al., 2001; Pencea et al., 2001).”
- Authors
- Benraiss, A., Chmielnicki, E., Lerner, K., Roh, D., & Goldman, S. A.
- Affiliations
- Cornell University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-09-01
- Volume
- 21
- Issue
- 17
- Pages
- 6718-6731
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763117
- OpenAlex
- W2123948067
- Cited by
- 540
- References
- 0
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 12 · 2021: 15 · 2020: 15 · 2019: 9 · 2018: 18 · 2017: 16 · 2016: 26 · 2015: 20 · 2014: 21 · 2013: 22 · 2012: 24
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society
- Regeneron Pharmaceuticals
- Multiple Sclerosis Society
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P50HL59312, P50HL059312)
- National Institute of Neurological Disorders and Stroke (R01-NS33106, R01NS029813, R01NS29813, R01NS033106)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- brain-derived neurotrophic factor, adult neurogenesis, neural progenitor cells, olfactory bulb, neostriatum, caudate-putamen, medium spiny neurons, adenoviral gene transfer, intraventricular injection, ependyma, viral vectors, neurotrophic factors, neural recruitment, DARPP-32, glutamic acid decarboxylase
- MeSH terms
- Adenoviridae, Animals, Bromodeoxyuridine, Cell Count, Cell Differentiation, Cell Line, Cell Movement, Cerebrospinal Fluid, Genetic Vectors, Humans, Immunohistochemistry, Injections, Intraventricular, Luminescent Proteins, Neurons, Olfactory Bulb, RNA, Messenger, Stem Cells, Tissue Distribution, Prosencephalon, Neostriatum, Rats, Sprague-Dawley, In Situ Hybridization, Genes, Reporter, Brain-Derived Neurotrophic Factor, Green Fluorescent Proteins, Rats
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