The DOI matches its Crossref record; 620 of the 625 references it cites were found in a registry or an index.
Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness
Open accessAbstract
Neuropeptide are auxiliary messenger molecules that always co-exist in nerve cells with one or more small-molecule (classic) neurotransmitters. Neuropeptides act both as transmitters and trophic factors, and play a role especially when the nervous system is challenged, as by injury, pain or stress. Here neuropeptides and coexistence in mammals are reviewed, but with special focus on the 29/30 amino acid galanin and its three receptors GalR1, -R2 and -R3. In particular, galanin’s role as a co-transmitter in both rodent and human noradrenergic locus coeruleus (LC) neurons is addressed. Extensive experimental animal data strongly suggest a role for the galanin system in depression–like behavior. The translational potential of these results was tested by studying the galanin system in human postmortem brains, first normal brains, and then by comparing five regions of brains obtained from depressed people who committed suicide, and from matched controls. It is hypothesized that, when exposed to severe stress, the noradrenergic LC neurons fire in bursts and release galanin from their soma/dendrites. Galanin then acts on somato-dendritic, inhibitory GalR3 autoreceptors, opening potassium channels and inhibiting firing. The purpose of these autoreceptors is to act as a ‘brake’ to prevent overexcitation, a brake that also is part of resilience to stress that protects against depression. Depression then arises when the inhibition is too strong and long lasting - a maladaption, allostatic load, leading to depletion of NA levels in the forebrain. It is suggested that disinhibition by a galanin GalR3 antagonist may have antidepressant activity by restituting forebrain NA levels. A role of galanin in depression is also supported by a recent candidate gene study, showing that variants in genes for galanin and its three receptors confer increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events. Taken together, the neuropeptide galanin, coexisting in LC neurons, may participate in the mechanism underlying resilience against a serious and common disorder, MDD. These results may lead to an increased understanding of how this illness develops which in turn can provide a basis for its treatment.
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“Diverse neuropeptides are expressed and released in regions of anxiety/fear neurocircuitries, often together with classical transmitters (Hökfelt et al., 2018).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Hökfelt et al., 2018
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Metadata
- Authors
- Hökfelt, T., Barde, S., Xu, Z.-Q. D., Kuteeva, E., Rüegg, J., Le Maitre, E., Risling, M., Kehr, J., Ihnatko, R., Theodorsson, E., Palkovits, M., Deakin, W., Bagdy, G., Juhasz, G., Prud’homme, H. J., Mechawar, N., Diaz-Heijtz, R., & Ögren, S. O.
- Affiliations
- Karolinska Institutet (SE)
- Linköping University (SE)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Hökfelt, Tomas
- ORCID
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2018-12-21
- Volume
- 12
- Pages
- 106-106
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC6309708
- OpenAlex
- W2906160505
- Cited by
- 139
- References
- 625
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 23 · 2023: 13 · 2022: 24 · 2021: 22 · 2020: 18 · 2019: 8 · 2018: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neural Circuits (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion, other-oa)
- DiVA (Linkoping University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Torsten Söderbergs Stiftelse
- National Alliance for Research on Schizophrenia and Depression
- Karolinska Institutet
- Vetenskapsrådet (04X-2887)
- Marcus och Amalia Wallenbergs minnesfond
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- neuropeptides, co-transmission, galanin, galanin receptors, locus coeruleus, noradrenergic neurons, depression, major depressive disorder, stress resilience, allostatic load, postmortem brain, suicide, antidepressant mechanism, childhood adversity, anxiety, coexistence of neurotransmitters
- MeSH terms
- Animals, Mental Disorders, Humans, Locus Coeruleus, Neuropeptides, Receptors, Neurotransmitter, Neurotransmitter Agents
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