The behavioral and biochemical effects of BDNF containing polymers implanted in the hippocampus of rats
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Brain-derived neurotrophic factor (BDNF) is closely linked with neuronal survival and plasticity in psychiatric disorders. In this work, we engineered degradable, injectable alginate microspheres and non-degradable, implantable poly(ethylene vinyl acetate) matrices to continuously deliver BDNF to the dorsal hippocampus of rats for two days or more than a week, respectively. The antidepressant-like behavioral effects of BDNF delivery were examined in the Porsolt forced swim test. Rats were sacrificed 10days after surgery and tissue samples were analyzed by western blot. A small dose of BDNF delivered in a single infusion, or from a two-day sustained-release alginate implant, produced an antidepressant-like behavior, whereas the same dose delivered over a longer period of time to a larger tissue region did not produce antidepressant-like effects. Prolonged delivery of BDNF resulted in a dysregulation of plasticity-related functions: increased dose and duration of BDNF delivery produced increased levels of TrkB, ERK, CREB, and phosphorylated ERK, while also producing decreased phosphorylated CREB. It is evident from this work that both duration and magnitude of BDNF dosing are of critical importance in achieving functional outcome.
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Experimental BDNF therapy has promising results in animal models of Alzheimer's disease, Parkinson's disease, and major depressive disorder.
“experimental therapy has been investigated in vivo and in vitro with promising results in animal models of AD [197], PD [198], and MDD [199]”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [199]
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- Authors
- Sirianni, R. W., Olausson, P., Chiu, A. S., Taylor, J. R., & Saltzman, W. M.
- Affiliations
- Yale University (US)
- Corresponding author
- Saltzman, W. Mark
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 1321
- Pages
- 40-50
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2834850
- OpenAlex
- W1974787539
- Cited by
- 51
- References
- 66
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 7
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ohio Department of Mental Health and Addiction Services
- National Institutes of Health (MH025642, MH066172, PHS DA011717, UL1-DE19586, NS45236, AA017537)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- brain-derived neurotrophic factor, alginate microspheres, dorsal hippocampus, antidepressant-like behavior, forced swim test, TrkB, ERK, CREB, neuroplasticity
- MeSH terms
- Alginates, Animals, Antidepressive Agents, Behavior, Animal, Biocompatible Materials, Depression, Drug Carriers, Hexuronic Acids, Hippocampus, Male, Microspheres, Neuronal Plasticity, Polyvinyls, Stress, Psychological, Blotting, Western, Drug Delivery Systems, Rats, Sprague-Dawley, Cyclic AMP Response Element-Binding Protein, Brain-Derived Neurotrophic Factor, Glucuronic Acid, Receptor, trkA, Extracellular Signal-Regulated MAP Kinases, Rats
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