Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain
Abstract
Vagus nerve stimulation therapy, effective for treatment-resistant epilepsy, has recently been approved also for treatment-resistant depression; nevertheless, the molecular mechanism(s) underlying its therapeutic action remains unclear. Given that neurotrophic factors and monoamines could play a crucial role in the pathophysiology of depression, we tested whether vagus nerve stimulation increases the expression of brain-derived neurotrophic factor, fibroblast growth factor, and nerve growth factor as well as the concentration of norepinephrine in the rat brain. Rats were implanted with a vagus nerve stimulator device and the effects of acute stimulation were evaluated on the growth factors mRNA levels and norepinephrine concentration by ribonuclease protection assay and microdialysis, respectively. We found that acute vagus nerve stimulation increased the expression of brain-derived neurotrophic factor and fibroblast growth factor in the hippocampus and cerebral cortex, decreased the abundance of nerve growth factor mRNA in the hippocampus, and, similar to the antidepressant drug venlafaxine, increased the norepinephrine concentration in the prefrontal cortex. This study demonstrates that acute vagus nerve stimulation triggers neurochemical and molecular changes in the rat brain involving neurotransmitters and growth factors known to play a crucial role in neuronal trophism. These new findings contribute to the elucidation of the molecular mechanisms underlying the therapeutic actions of vagus nerve stimulation in both treatment-resistant depression and epilepsy.
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VNS increases the NE concentration in the prefrontal cortex.
“Thus, VNS was shown to increase the NE concentration in the prefrontal cortex (95).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [95]
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- Authors
- Follesa, P., Biggio, F., Gorini, G., Caria, S., Talani, G., Dazzi, L., Puligheddu, M., Marrosu, F., & Biggio, G.
- Affiliations
- University of Cagliari (IT)
- Corresponding author
- Follesa, Paolo
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 1179
- Pages
- 28-34
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2079370219
- Cited by
- 352
- References
- 59
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 30 · 2023: 26 · 2022: 26 · 2021: 30 · 2020: 26 · 2019: 25 · 2018: 24 · 2017: 29 · 2016: 15 · 2015: 11 · 2014: 9 · 2013: 9 · 2012: 14
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- vagus nerve stimulation, norepinephrine, brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, neurotrophic factors, gene expression, hippocampus, cerebral cortex, prefrontal cortex, venlafaxine, treatment-resistant depression, drug-resistant epilepsy, monoamines
- MeSH terms
- Animals, Cerebral Cortex, Data Interpretation, Statistical, Electric Stimulation, Male, Norepinephrine, RNA, Messenger, Vagus Nerve, Gene Expression, Fibroblast Growth Factor 2, Rats, Sprague-Dawley, Microdialysis, Brain-Derived Neurotrophic Factor, Nuclease Protection Assays, Rats
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