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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Galanin Receptor/Neuropeptide Y Receptor Interactions in the Central Nervous System
Dı́az-Cabiale, Z., Flores‐Burgess, A., Parrado, C., Narváez, M., Millón, C., Puigcerver, A., Coveñas, R., Fuxé, K., & Narváez, J. Á. (2014) · Current Protein and Peptide Science · doi:10.2174/1389203715666140901111709 · Cited by 14
Proceedings: Does the giant cerebral neurone of Helix release two transmitters: ACh and serotonin?
Cottrell, G. A. (1976) · PubMed · Cited by 14
Silote, G. P., Rosal, A. B., de Souza, M. M., & Beijamini, V. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.06.023 · Cited by 13
Control of adenohypophysial functions by peptides of the central nervous system.
Guillemin, R. (1978) · PubMed · Cited by 13
Tyrosine Hydroxylase Activity in Discrete Brain Regions of Depression Model Rats
Komori, T., Nomura, J., Inoue, K., & Kitayama, I. T. (1990) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.1990.tb01654.x · Cited by 12
In vitro toxicity of the galanin receptor 3 antagonist SNAP 37889
Koller, A., Rid, R., Beyreis, M., Bianchini, R., Holub, B. S., Lang, A., Sternberg, F., Brodowicz, B., Velickovic, O., Jakab, M., et al. (2015) · Neuropeptides · doi:10.1016/j.npep.2015.12.003 · Cited by 12
Chronic venlafaxine treatment fails to alter the levels of galanin system transcripts in normal rats
Petschner, P., Juhász, G., Tamási, V., Ádori, C., Tóthfalusi, L., Hökfelt, T. G. M., & Bagdy, G. (2016) · Neuropeptides · doi:10.1016/j.npep.2016.01.010 · Cited by 12
Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders
Xiao, X., Wang, L., Wang, C., Yuan, T., Zhou, D., Zheng, F., Li, L., Grigoroiu‐Serbânescu, M., Ikeda, M., Iwata, N., et al. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0019-0 · Cited by 12
Validation of antibody-based tools for galanin research
Brunner, S. M., Koller, A., Stockinger, J., Sternberg, F., Leis, S., Ernst, F., Strasser, P., Brodowicz, B., Ebner, S., Holub, B. S., et al. (2018) · Peptides · doi:10.1016/j.peptides.2018.08.010 · Cited by 12
Chapter 4.1 Peptide receptor ligands to treat anxiety disorders
Steckler, T. (2008) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(07)00010-0 · Cited by 10
Galanin in Glia: Expression and Potential Roles in the CNS
Butzkueven, H., & Gundlach, A. L. (2010) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0346-0228-0_6 · Cited by 9
Proceedings: Coexistence of monoamines in adrenergic synaptic vesicles.
Jaim-Etcheverry, G., & Lm, Z. (1973) · PubMed · Cited by 7
GAL3 receptor knockout mice exhibit an alcohol‐preferring phenotype
Genders, S. G., Scheller, K. J., Jaehne, E. J., Turner, B. J., Lawrence, A. J., Brunner, S. M., Kofler, B., van den Buuse, M., & Djouma, E. (2018) · Addiction Biology · doi:10.1111/adb.12641 · Cited by 7
Short N-terminal galanin fragments are occurring naturally in vivo
Ihnatko, R., & Theodorsson, E. (2017) · Neuropeptides · doi:10.1016/j.npep.2017.03.005 · Cited by 5
Hökfelt, T. (2010) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0346-0228-0 · Cited by 5
Alterations in the serotonergic and substance P systems in posttraumatic stress disorder
Frick, A., Åhs, F., Palmquist, Å. M., Pissiota, A., Wallenquist, U., Fernandez, M., Jonasson, M., Appel, L., Frans, Ö., Lubberink, M., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.159 · Cited by 4
Chapter 10 Co-existence of chemical messengers in neurons
Jaim-Etcheverry, G. (1994) · Progress in brain research · doi:10.1016/s0079-6123(08)60771-2 · Cited by 3
Yeterian (1998) · doi:10.1002/(sici)1096-9861(19980928)399:3
Flagged first, then by citations
5 of the 625 references couldn’t be matched to a known paper.
Research works printed but not linked: 10
- Bremner, Noradrenergic mechanisms in stress and anxiety: II. Clinical studies., Synapse, 23, 39, 10.1002/(SICI)1098-2396(199605)23:1<39::AID-SYN5>3.0.CO;2-I · DOI
- Fuxe, 1998, Galanin modulates 5-Hydroxytryptamine functions. Focus on Galanin and Galanin Fragment/
- Hokfelt, 1986, Coexistence of neuronal messengers: a new principle in chemical transmission., Prog. Brain Res., 68, 1
- Hokfelt, 1984, “Central catcholamine neurons as revelaed by immunohistochemistry with special reference to adrenaline neurons,” in, Handbook of Chemical Neuroanatomy. Vol. 2: Classical Transmitters in the CNS, 157
- Maes, 1995, “The serotonin hypothesis of major depression,” in, Psychopharmacology: The Fourth Generation of Progress, 933
- Mutt, 1989, Hormonal Peptides, Fidia Research Foundation Neuroscience Award Lectures., 125
- O’Donnell, 2003, “Localization of galanin receptor subtypes in the rat CNS,” in, Handbook of Chemical Neuroanatomy, 195
- Schatzberg, 1995, “Recent studies on norepinephrine systems im mood disorders,” in, Psychopharmacology: The Fourth Generation of Progress, 911
- Ungerstedt, 1984, Measurement of neurotransmitter release by intracranial dialysis., Methods Neurosci., 6, 81
- 2013, Mental Health and Older Adults.
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Sartori, S. B., & Singewald, N. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107402 · Cited by 236
The physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168
Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect
Chen, W.-C., Liu, Y., Liu, W.-F., Zhou, Y., He, H., & Lin, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580378 · Cited by 140
VGF as a biomarker and therapeutic target in neurodegenerative and psychiatric diseases
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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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