Galanin/5-HT Receptor Interactions. A New Integrative Mechanism in the Control of 5-HT Neurotransmission in the Central Nervous System

Fuxé, Kjell; Agnati, Luigi F.; Euler, Gabriel von; Lundgren, K. D.; Zoli, Michèle; Bjelke, Börje; Eneroth, P.; Ögren, S.O.

doi:10.1007/978-94-009-1912-9_23

Cited by 17 publications

(29 citation statements)

References 29 publications

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“…However, in rat TRH coexists to a large extent with NPY and also with neurotensin; in fact, some neurons contain all three peptides (Tsuruo et al, 1988). The (surprising) virtual lack of galanin þ neurons in the mouse vPAG confirms earlier findings (Cheung et al, 2001;Perez et al, 2001;Larm et al, 2003;Kuteeva et al, 2004), contrasting the rat DRN, where many 5-HT neurons colocalize galanin (Melander et al, 1986b;Fuxe et al, 1990;Xu and Hökfelt, 1997).…”

Section: Peptide Transmitters In the Vpagsupporting

confidence: 85%

Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain

Maître

Fabre

et al. 2010

J of Comparative Neurology

161

141

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Serotonin neurons play a major role in many normal and pathological brain functions. In the rat these neurons have a varying number of cotransmitters, including neuropeptides. Here we studied, with histochemical techniques, the relation between serotonin, some other small-molecule transmitters, and a number of neuropeptides in the dorsal raphe nucleus (DRN) and the adjacent ventral periaqueductal gray (vPAG) of mouse, an important question being to establish possible differences from rat. Even if similarly distributed, the serotonin neurons in mouse lacked the extensive coexpression of nitric oxide synthase and galanin seen in rat. Although partly overlapping in the vPAG, no evidence was obtained for the coexistence of serotonin with dopamine, substance P, cholecystokinin, enkephalin, somatostatin, neurotensin, dynorphin, thyrotropin-releasing hormone, or corticotropin-releasing hormone. However, some serotonin neurons expressed the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD). Work in other laboratories suggests that, as in rat, serotonin neurons in the mouse midline DRN express the vesicular glutamate transporter 3, presumably releasing glutamate. Our study also shows that many of the neuropeptides studied (substance P, galanin, neurotensin, dynorphin, and corticotropin-releasing factor) are present in nerve terminal networks of varying densities close to the serotonin neurons, and therefore may directly or indirectly influence these cells. The apparently low numbers of coexisting messengers in mouse serotonin neurons, compared to rat, indicate considerable species differences with regard to the chemical neuronatomy of the DRN. Thus, extrapolation of DRN physiology, and possibly pathology, from rat to mouse, and even human, should be made with caution.

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Section: Peptide Transmitters In the Vpagsupporting

confidence: 85%

Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain

Maître

Fabre

et al. 2010

J of Comparative Neurology

161

141

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“…3 D and I) harbors a large number of 5-HT neurons in the rat (101-103), and distinct rostrocaudal differences in function exist (104). In the rat, many of the 5-HT neurons express galanin (20,(22)(23)(24). However, a large number of nonserotonin cells exist in the rodent DR, with different electrophysiological characteristics (105)(106)(107) and neurotransmitter phenotypes, including GABA-, glutamate-, and peptidergic neurons, constituting some 50-70% of all DR neurons (70,(108)(109)(110)(111)(112)(113)(114).…”

Section: Discussionmentioning

confidence: 99%

“…Galanin is a 29-aa (30-aa in humans) neuropeptide (18) with a wide distribution in the rat brain (19,20), where it is coexpressed with noradrenaline/norepinephrine (NA) in locus coeruleus (LC) neurons and with 5-hydroxytryptamine (5-HT) in dorsal raphe nucleus (DR) neurons (21)(22)(23)(24)(25). There are three galanin receptors, GALR1-GALR3, which all belong to the family of seven transmembrane-spanning, G protein-coupled receptors (26)(27)(28)(29).…”

mentioning

confidence: 99%

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Wang

Barde

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects.dorsal raphe | neuropeptide | siRNA | stress | transmitter coexistence T he indoleamine hypothesis of depression was formulated some five decades ago (1, 2), in parallel with the catecholamine hypothesis (3, 4), and has been supported by the success of selective serotonin reuptake inhibitors (SSRIs) for treatment of major depression (MD) (5). However, in a considerable number of cases, SSRIs are associated with side effects or lack of efficacy. For example, after treatment with SSRIs, only one-third of patients obtain full remission of symptoms (6). Therefore, there is an ongoing search for new medications targeting mood disorders, such as MD and anxiety. Here, neuropeptides and their receptors, the most diverse family of neurotransmitters in the brain (7), have been extensively explored (5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), including galanin and its three receptors.Galanin is a 29-aa (30-aa in humans) neuropeptide (18) with a wide distribution in the rat brain (19,20), where it is coexpressed with noradrenaline/norepinephrine (NA) in locus coeruleus (LC) neurons and with 5-hydroxytryptamine (5-HT) in dorsal raphe nucleus (DR) neurons (21-25). There are three galanin receptors, GALR1-GALR3, which all belong to the family of seven transmembrane-spanning, G protein-coupled receptors (26-29). They are found in many areas of the rat brain, as first shown with autoradiographic ligand-binding methodology (30, 31), and later with in situ hybridization (ISH)/quantitative real-time PCR (qPCR) (32-36). The galanin system has been associated with numerous physiological and pathophysiological functions (29), including depression-and anxiety-like behaviors.There is early evidence from studies on the rat that central administration of galanin influences mood-related behavior in a region-specific way (37, 38), and also that galanin is prodepres...

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“…In particular, it coexists with NA in the locus coeruleus in both rat (27)(28)(29) and human (26,(30)(31)(32) and in rat with 5-HT in the dorsal raphe nucleus (28,33,34).…”

mentioning

confidence: 99%

Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

Barde

Rüegg

Prud’homme

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL 1-3 , are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls. Transcripts for all four members were detected and showed marked regional variations, GAL and galanin receptor 1 (GALR1) being most abundant. Striking increases in GAL and GALR3 mRNA levels, especially in the noradrenergic locus coeruleus and the dorsal raphe nucleus, in parallel with decreased DNA methylation, were found in both male and female suicide subjects as compared with controls. In contrast, GAL and GALR3 transcript levels were decreased, GALR1 was increased, and DNA methylation was increased in the dorsolateral prefrontal cortex of male suicide subjects, however, there were no changes in the anterior cingulate cortex. Thus, GAL and its receptor GALR3 are differentially methylated and expressed in brains of MDD subjects in a region-and sex-specific manner. Such an epigenetic modification in GALR3, a hyperpolarizing receptor, might contribute to the dysregulation of noradrenergic and serotonergic neurons implicated in the pathogenesis of MDD. Thus, one may speculate that a GAL 3 antagonist could have antidepressant properties by disinhibiting the firing of these neurons, resulting in increased release of noradrenaline and serotonin in forebrain areas involved in mood regulation.epigenetics | human postmortem brain | neuropeptides | stress | transmitter coexistence

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Galanin/5-HT Receptor Interactions. A New Integrative Mechanism in the Control of 5-HT Neurotransmission in the Central Nervous System

Cited by 17 publications

References 29 publications

Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain

Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

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