Life without brain serotonin: Reevaluation of serotonin function with mice deficient in brain serotonin synthesis

Mosienko, Valentina; Beis, Daniel; Pasqualetti, Massimo; Waider, Jonas; Matthes, Susann; Qadri, Fatimunnisa; Bäder, Michael; Alenina, Natalia

doi:10.1016/j.bbr.2014.06.005

Cited by 100 publications

(86 citation statements)

References 92 publications

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“…In this context, the fact that a live without (brain) serotonin is possible is more likely to stimulate further research than giving a definite answer [380]. It does, however, suggest that brain serotonin, at least with regard to satiety, might have a modulating function.…”

Section: Serotonin and Satiety -What Is Next?mentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

257

167

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Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

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Section: Serotonin and Satiety -What Is Next?mentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

257

167

View full text Add to dashboard Cite

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“…Here, we measured BDNF protein levels in Tph2 -/-mice that lack brain serotonin (and show certain features of depression-like behaviors such as impaired maternal care and increased immobility in the Porsolt forced swim test; reviewed in [14]), and SERT -/-mice, which exhibit increased extracellular serotonin levels [15,16] despite an overall reduction (60 to 80%) in serotonin tissue concentrations [17].…”

Section: Introductionmentioning

confidence: 99%

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Kronenberg

Mosienko

Gertz

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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The interplay between BDNF signaling and the serotonergic system remains incompletely understood. Using a highly sensitive enzyme-linked immunosorbent assay, we studied BDNF concentrations in hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 -/-) mice lacking brain serotonin and serotonin transporter (SERT) deficient (SERT -/-) mice lacking serotonin re-uptake. Surprisingly, hippocampal BDNF was significantly elevated in Tph2 -/-mice, whereas no significant changes were observed in SERT -/-mice. Furthermore, BDNF levels were increased in the prefrontal cortex of Tph2 -/-but not of SERT -/-mice. Our results emphasize the interaction between serotonin signaling and BDNF. Complete lack of brain serotonin induces BDNF expression.

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“…In several cases, other groups have been unable to independently replicate these findings. These cases include studies involving brain serotonin metabolism, [28][29][30] bone phenotypes in mice with disrupted leptin signaling, 10,[31][32][33][34] bone phenotypes in mice with KOs of b-adrenergic receptors [35][36][37] and actions of osteocalcin on glucose metabolism and diabetes. [38][39][40] Potential explanations for observations of distinct phenotypes in similar mouse models include, but are not limited to, environmental conditions, age, genetic backgrounds and diets.…”

Section: Discussionmentioning

confidence: 99%

“…7 The multiple phenotypes observed in Tph1 and Tph2 KO mice have been elegantly reviewed. [8][9][10] Decreased trabecular bone mass in spine and femur has been reported in growing Tph2 KO mice. 11 This laboratory 12 previously reported that disruption of Tph1 in mice resulted in high trabecular bone mass at 4 to 12 weeks of age by removing the normal suppression of bone formation promoted by gutderived circulating serotonin.…”

Section: Introductionmentioning

confidence: 99%

Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness

Brommage¹,

Liu²,

Doree³

et al. 2015

BoneKEy Reports

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Disruption of serotonin synthesis in neurons and the periphery by knockout (KO) of mouse genes for tryptophan hydroxylases (peripheral Tph1 and neuronal Tph2) has been claimed to decrease (Tph2 KO) and increase (Tph1 KO) bone mass. In this report, adult male and female Tph2 KO mice were observed to have elevated spine trabecular bone. Female Tph2 KO mice have reduced midshaft femur cortical bone thickness. Bone mass was normal in male and female Tph1 KO mice examined as part of a Tph1/Tph2 double knockout (DKO) mouse cohort.

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Life without brain serotonin: Reevaluation of serotonin function with mice deficient in brain serotonin synthesis

Cited by 100 publications

References 92 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness

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