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Role of neurotrophic factors in depression
Abstract
Major depression is associated with reduced volumes in the hippocampus and prefrontal cortex, whereas antidepressant treatments promote several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation, in the hippocampus. Several neurotrophic factors are associated with depression or antidepressant action. Stress suppresses brain-derived neurotrophic factor (BDNF) synthesis in the hippocampus, at least partially through a sustained modification of chromatin structure. Essentially all antidepressant treatments increase BDNF synthesis and signaling in the hippocampus and prefrontal cortex. This signaling is required for the behavioral effects of antidepressant drugs in rodents, and increased BDNF levels in the hippocampus mimic the behavioral effects of antidepressants. However, injection of BDNF into the mesolimbic dopamine pathway produces an opposing depression-like response. One hypothesis emerging from these data proposes that mood disorders reflect failed function of critical neuronal networks, whereas a gradual network recovery through activity-dependent neuronal plasticity induces the antidepressant effect. Neurotrophic factors themselves do not control mood, but they act as necessary tools in the activity-dependent modulation of networks, the physiological function of which determines how a plastic change influences mood.
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“These results lend substantial support to the neuroplasticity hypothesis of depression (sometimes referred to as the neurotrophin hypothesis) (11, 23–36).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [28]
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“A growing body of research suggests that neuroplasticity pathways play a significant role in the pathophysiology of depression and in the therapeutic mechanisms of antidepressant drugs (AD) [1,2,3].”
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Metadata
- Authors
- CASTREN, E., VOIKAR, V, & RANTAMAKI, T.
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 7
- Issue
- 1
- Pages
- 18-21
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W1993636230
- Cited by
- 667
- References
- 32
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 17 · 2023: 20 · 2022: 13 · 2021: 24 · 2020: 30 · 2019: 23 · 2018: 31 · 2017: 32 · 2016: 33 · 2015: 57 · 2014: 38 · 2013: 40 · 2012: 59
- FWCI
- 25.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- neurotrophic factors, major depressive disorder, brain-derived neurotrophic factor, antidepressant mechanism, hippocampus, prefrontal cortex, neuroplasticity, neurogenesis, synaptogenesis, chronic stress, chromatin structure, mesolimbic dopamine system, activity-dependent plasticity, mood disorders
- MeSH terms
- Animals, Antidepressive Agents, Depression, Humans, Nerve Growth Factors, Stress, Physiological, Mood Disorders
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