Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats

Galindo, Lígia Cristina Monteiro; Barros, Manuella da Luz Duarte; Pinheiro, Isabeli Lins; Santana, Ricardo Vinicius de Carvalho; Matos, Rhowena Jane Barbosa de; Leandro, Carol Góis; Souza, Sandra Lopes de; Castro, Raul Manhães de

doi:10.1016/j.ijdevneu.2015.07.004

Cited by 16 publications

(8 citation statements)

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“…Alternatively, decreased weight of low-5HT pups may be a consequence of their own 5HT phenotype, similarly to transgenic 5HTT-overexpressing mice with reduced extracellular 5HT, who are smaller and lighter than their wild-type littermates (Pringle et al, 2008). Literature findings on the long-term effects of pharmacologically induced rise in 5HT availability during development on the body weight of animals are rather inconsistent, showing either increased, decreased, or normal body weight in later life (Grzeskowiak et al, 2012;Galindo et al, 2015;De Long et al, 2015). Increased susceptibility to adult obesity was related, among other possible factors, to dysregulation of hypothalamic 5HT system during development (Martin-Gronert et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

et al. 2020

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Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert opposite effects on the body weight regulation: increase in brain 5HT activity is expected to decrease body weight, whereas increase in peripheral 5HT activity will increase body weight and adiposity. In a genetic model of rats with constitutionally highor low-5HT homeostasis (hyperserotonergic/hyposerotonergic rats), we have studied how individual differences in endogenous 5HT tone modulate net energy balance of the organism. The high-5HT and low-5HT sublines of the model were developed by selective breeding toward extreme platelet activities of 5HT transporter, a key molecule determining 5HT bioavailability/activity. In animals from high-5HT and low-5HT sublines, we assessed physiological characteristics associated with body weight homeostasis and expression profile of a large scale of body weight-regulating genes in hypothalamus, a major brain region controlling energy balance. Results showed that under standard chow diet animals from the high-5HT subline, as compared to low-5HT animals, have lifelong increased body weight (by 12%), higher absolute daily food intake (by 9%), and different pattern of fat distribution (larger amount of white adipose tissue and lower amount of brown adipose tissue). A large number of body weight-regulating hypothalamic genes were analyzed for their mRNA expression: 24 genes by reverse transcription-quantitative polymerase chain reaction (n = 9-10 rats/subline) including neuropeptides and their receptors, growth factors, transcriptional factors, and receptors for peripheral signals, and a total of 84 genes of various classes by polymerase chain reaction array (pools of six rats/subline). Only few genes showed significant differences in mRNA expression levels between 5HT sublines (e.g. neuropeptide Y receptor, fibroblast growth factor 10), but high-5HT animals displayed a clear trend to upregulation of mRNAs for a number of orexigenic signaling peptides, their receptors, and other molecules with orexigenic activity. Receptors for peripheral signals (leptin, insulin) and molecules in their downstream signaling were not altered, indicating no changes in central insulin/leptin resistance. At the protein level, there were no differences in the Frontiers in Neuroscience | www.frontiersin.org 1 March 2020 | Volume 14 | Article 219 Kesić et al. Serotonin and Body Weight Regulationcontent of hypothalamic leptin receptor between 5HT sublines, but significant sex and age effects were observed. Results show that higher constitutive/individual 5HT tone favors higher body weight and adiposity probably due to concurrent upregulation of several hypothalamic orexigenic pathways.

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Section: Discussionmentioning

confidence: 99%

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

et al. 2020

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“…The serotonin system consists of 15 different receptors that are key players at crucial neurodevelopmental stages, regulating neurogenesis, apoptosis, axon branching and dendritogenesis 11 . Many of the studies included in the synthesis of evidence in the current review, which have been selected on the presence of behavioral outcomes, also include outcomes reflecting brain health from the global to the molecular level: the corticosterone response to stress 74, 81, 96, 100, 123, 124, 126, 130, 135 , brain structure and connectivity 71, 77, 84, 93, 101, 110, 122 , neuronal health 59, 82, 85, 89, 104, 109, 111, 126, 135 , monoamine concentrations in the brain 43, 44, 46, 59, 105, 116, 117, 133, 135, 140, 141 , protein expression in the brain – mainly related to the serotonergic system and neurogenesis 62, 71, 78, 88, 91, 97, 127, 129, 141 , gene expression 76, 94, 96, 112, 113, 120, 121, 123, 137, 141, 143 , and epigenetic modifications 76, 112, 114, 124 .…”

Section: Discussionmentioning

confidence: 99%

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

Ramsteijn

Wijer

Rando

et al. 2019

Preprint

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AbstractIn the Western world, 2-5% of pregnant women use selective serotonin reuptake inhibitor (SSRI) antidepressants. There is no consensus on the potential long-term neurodevelopmental outcomes of early SSRI exposure. Our aim was to determine whether there is an overall effect of perinatal SSRI exposure in animals on a spectrum of behavioral domains. After a comprehensive database search in PubMed, PsycINFO, and Web of Science, we included 99 publications. We performed nine meta-analyses and two qualitative syntheses corresponding to different behavioral categories, aggregating data from thousands of animals. We found evidence for reduced activity and exploration behavior (standardized mean difference (SMD) −0.28 [-0.38, −0.18]), more passive stress coping (SMD −0.37 [-0.52, −0.23]), and less efficient sensory processing (SMD −0.37 [-0.69, −0.06]) in SSRI-versus vehicle-exposed animals. No differences were found for anxiety (p=0.06), social behavior, learning and memory, ingestive- and reward behavior, motoric behavior, or reflex and pain sensitivity. Exposure in the period equivalent to the human third trimester was associated with the strongest effects.HighlightsPerinatal SSRI exposure in rodents alters outcomes in three behavioral domains.It leads to reduced activity, passive stress coping, and weaker sensory processing.Females are understudied but seem to be less vulnerable than males.Early postnatal exposure in rodents leads to the largest effects on behavior.This is equivalent to the third trimester of pregnancy in humans.

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“…Exposure to selective serotonin reuptake inhibitors during lactation reduces body weight and food intake [3,46]. The use of citalopram during lactation decreased growth and delayed the maturation of rodents' physical characteristics [47].…”

Section: Serotonin and Food Intakementioning

confidence: 99%

“…The body weight of rodents exposed to fluoxetine was 22% lower at age 21 days [46]. The low body weight phenotype persisted to adulthood in neonatal animals exposed to fluoxetine [3]. In rodents, fluoxetine increases serotonin, stimulating satiety, which reduces food intake and body weight [33].…”

Section: Serotonin and Food Intakementioning

confidence: 99%

“…Serotonin or 5-Hydroxytryptamine (5-HT) and Serotonin Transporter (SERT) are essential for nervous system ontogenesis and maturation [1]. Environmental factors, such as malnutrition, selective serotonin reuptake inhibition, and changes in the expression of the serotonin transporter gene during the early stages of development may increase central serotonin availability, delay in satiety the trigger associated with hyperphagia, and reduce its anorexigenic effects in adult organisms [2][3][4]. However, despite the numerous studies conducted in recent years, the origin of the physiological and molecular mechanisms controlled by the serotonergic system has not been totally clarified.…”

Section: Introductionmentioning

confidence: 99%

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Perinatal serotonergic activity: A decisive factor in the control of food intake

et al. 2017

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The serotoninergic system controls key events related to proper nervous system development. The neurotransmitter serotonin and the serotonin transporter are critical for this control. Availability of these components is minutely regulated during the development period, and the environment may affect their action on the nervous system. Environmental factors such as undernutrition and selective serotonin reuptake inhibitors may increase the availability of serotonin in the synaptic cleft and change its anorectic action. The physiological responses promoted by serotonin on intake control decrease when requested by acute stimuli or stress, demonstrating that animals or individuals develop adaptations in response to the environmental insults they experience during the development period. Diseases, such as anxiety and obesity, appear to be associated with the body’s response to stress or stimulus, and require greater serotonergic system action. These findings demonstrate the importance of the level of serotonin in the perinatal period to the development of molecular and morphological aspects of food intake control, and its decisive role in understanding the possible environmental factors that cause diseases in adulthood.

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Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats

Abstract: These findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats.

Cited by 16 publications

References 35 publications

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

Perinatal serotonergic activity: A decisive factor in the control of food intake

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