Galanin/5-HT interactions in the rat central nervous system. Relevance for depression

Fuxe, K.; Hedlund, Peter B.; Euler, Gabriel von; Lundgren, K. D.; Martire, Maria; Ögren, Sven Ove; Eneroth, P.; Agnati, Luigi F.

doi:10.1007/978-1-349-12664-4_16

Cited by 26 publications

(29 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B 370: 20140183 the concept of using serotonin selective reuptake inhibitors (SSRIs) in the treatment of depression [111]. Much later on, the 5-HT isoreceptor disbalance hypothesis of depression was introduced [112] based inter alia on our observations in 1977, for example that amitryptilin blocks head twitches correlating with its ability to displace d-LSD from its binding sites. However, amitryptilin did not displace 5-HT from its binding sites.…”

Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 99%

See 1 more Smart Citation

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto-Escuela

Agnati

Bechter

et al. 2015

Phil. Trans. R. Soc. B

113

130

View full text Add to dashboard Cite

One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (point-to-point communication, the prototype being synaptic transmission with axons and terminals) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid (CSF)) involving large numbers of cells in the CNS. Volume and synaptic transmission become integrated inter alia through the ability of their chemical signals to activate different types of receptor protomers in heteroreceptor complexes located synaptically or extrasynaptically in the plasma membrane. The demonstration of extracellular dopamine (DA) and serotonin (5-HT) fluorescence around the DA and 5-HT nerve cell bodies with the Falck-Hillarp formaldehyde fluorescence method after treatment with amphetamine and chlorimipramine, respectively, gave the first indications of the existence of VT in the brain, at least at the soma level. There exist different forms of VT. Early studies on VT only involved spread including diffusion and flow of soluble biological signals, especially transmitters and modulators, a communication called extrasynaptic (short distance) and long distance (paraaxonal and paravascular and CSF pathways) VT. Also, the extracellular vesicle type of VT was demonstrated. The exosomes (endosome-derived vesicles) appear to be the major vesicular carriers for VT but the larger microvesicles also participate. Both mainly originate at the soma-dendritic level. They can transfer lipids and proteins, including receptors, Rab GTPases, tetraspanins, cholesterol, sphingolipids and ceramide. Within them there are also subsets of mRNAs and non-coding regulatory microRNAs. At the soma-dendritic membrane, sets of dynamic postsynaptic heteroreceptor complexes (built up of different types of physically interacting receptors and proteins) involving inter alia G protein-coupled receptors including autoreceptors, ion channel receptors and receptor tyrosine kinases are hypothesized to be the molecular basis for learning and memory. At nerve terminals, the presynaptic heteroreceptor complexes are postulated to undergo plastic changes to maintain the pattern of multiple transmitter release reflecting the firing pattern to be learned by the heteroreceptor complexes in the postsynaptic membrane.

show abstract

Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 99%

“…This suggested that depression may be produced by a disbalance in the activity of 5-HT receptor subtypes some of which contribute to the development of depression, like 5-HT2A and 5-HT7, while others, like 5-HT1A and 5-HT4, contribute to antidepressant actions [112].…”

Section: (B) the Integration Of Synaptic And Volume Transmission Signalsmentioning

confidence: 99%

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto-Escuela

Agnati

Bechter

et al. 2015

Phil. Trans. R. Soc. B

113

130

View full text Add to dashboard Cite

show abstract

“…It has been proposed, based on animal experiments over the last few decades, that neuropeptide also receptors are putative targets for development of antidepressants, including receptors for substance P, neuropeptide tyrosine, corticotropin-releasing factor/ corticotropin-releasing hormone, melanocyte-concentrating hormone, vasopressin, and dynorphin (138)(139)(140)(141)(142)(143), as well as the galanin system. Thus, galanin interacts with 5-HT1A receptors, and galanin antagonists and agonists have anxiolytic and antidepressive effects in animal experiments (144)(145)(146)(147)(148)(149)(150)(151). Interestingly, association of genes encoding galanin and/or GalR3 has been reported for psychiatric phenotypes (152)(153)(154), including panic disorder (155), depression-related parameters (156)(157)(158), and nicotine dependence (159,160).…”

Section: Significancementioning

confidence: 99%

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Maître

Barde

Palkovits

et al. 2013

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

View full text Add to dashboard Cite

Using riboprobe in situ hybridization, we studied the localization of the transcripts for the neuropeptide galanin and its receptors (GalR1-R3), tryptophan hydroxylase 2, tyrosine hydroxylase, and nitric oxide synthase as well as the three vesicular glutamate transporters (VGLUT 1-3) in the locus coeruleus (LC) and the dorsal raphe nucleus (DRN) regions of postmortem human brains. Quantitative real-time PCR (qPCR) was used also. Galanin and GalR3 mRNA were found in many noradrenergic LC neurons, and GalR3 overlapped with serotonin neurons in the DRN. The qPCR analysis at the LC level ranked the transcripts in the following order in the LC: galanin >> GalR3 >> GalR1 > GalR2; in the DRN the ranking was galanin >> GalR3 >> GalR1 = GalR2. In forebrain regions the ranking was GalR1 > galanin > GalR2. VGLUT1 and -2 were strongly expressed in the pontine nuclei but could not be detected in LC or serotonin neurons. VGLUT2 transcripts were found in very small, nonpigmented cells in the LC and in the lateral and dorsal aspects of the periaqueductal central gray. Nitric oxide synthase was not detected in serotonin neurons. These findings show distinct differences between the human brain and rodents, especially rat, in the distribution of the galanin system and some other transmitter systems. For example, GalR3 seems to be the important galanin receptor in both the human LC and DRN versus GalR1 and -2 in the rodent brain. Such knowledge may be important when considering therapeutic principles and drug development.he locus coeruleus (LC) and the dorsal raphe nucleus (DRN)/raphe median nucleus (MRN) have been the focus of clinical and preclinical monoamine research for almost half a century. Using the formaldehyde fluorescence (Falck-Hillarp) method (1), Dahlström and Fuxe (2) originally described these nuclei in the rat as containing noradrenaline (NA) (the A6 group) and 5-hydroxytryptamine (5-HT; serotonin) (the B7/8 groups), respectively. The LC harbors 2,800-3,600 neurons with an additional 260 neurons in the subcoeruleus area, the great majority of which are noradrenergic (3-6).The DRN forms a rostro-caudal, ventral midline column and is part of the periaqueductal central gray (PAG) (7) with a large number of 5-HT neurons that can be subdivided into several subgroups (2,(8)(9)(10)(11). Both the NA-LC (5, 6, 12) and the 5HT-DRN (8-11, 13) neurons have wide projections to most forebrain areas.In humans the LC is a compact, blue-pigmented nucleus consisting of a total of ∼50,000 neurons (both sides), almost all of which are noradrenergic (14-16). The DRN comprises about 165,000 5-HT neurons, which constitute around 70% of all DRN neurons (17). Thus, there are numerous nonserotonergic neurons in the human DRN, as is also the case in other species, including the mouse (18,19).It now is well established that most neurons synthesize and release several types of messenger molecules in the process known as "cotransmission" (20-26). For example, in the rat some serotonergic DRN neurons synthesize nitric oxide (NO), visualized as N...

show abstract

“…A dysregulation of the 5-HT1A autoreceptors leading to a marked reduction of the firing rate in the ascending raphe-forebrain 5-HT neurons has been implicated in major depression (Albert et al, 2011). It seems possible that a certain balance of activity at different postjunctional 5-HT receptor subtypes of the seven 5-HT receptor families identified (Hoyer et al, 2002) needs to be developed with time through adaptive changes to counteract the depression (Fuxe et al, 1991). In fact, certain antidepressant drugs may as part of their action block certain 5-HT2-like receptors (Fuxe et al, 1977;Ogren et al, 1979;Snyder, 1979, 1980).…”

Section: Introductionmentioning

confidence: 99%

The Existence of FGFR1–5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity

et al. 2012

Self Cite

View full text Add to dashboard Cite

Galanin/5-HT interactions in the rat central nervous system. Relevance for depression

Cited by 26 publications

References 19 publications

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

The Existence of FGFR1–5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity

Contact Info

Product

Resources

About