Hyperserotonemia in autism: activity of 5HT-associated platelet proteins

Hranilović, Dubravka; Bujas-Petković, Zorana; Tomičić, Maja; Bordukalo-Niksic, Tatjana; Blažević, Sofia Ana; Čičin‐Šain, Lipa

doi:10.1007/s00702-009-0192-2

Cited by 46 publications

(32 citation statements)

References 58 publications

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“…A number of studies have specifically examined gene expression patterns in ASD [90][91][92][114][115][116][117][118][119][120][121][122][123]. It should be noted that predating this gush of expression studies in ASD, hyperserotonemia was observed in one third of patients and platelet serotonin was suggested as a marker for this disorder [124][125][126][127].…”

Section: Biomarkers For Autism Spectrum Disordersmentioning

confidence: 99%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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Edited by Sergio Papa, Gianfranco Gilardi and Wilhelm JustKeywords: Autism spectrum disorder (ASD) All-trans retinoic acid (ATRA) CD38 Oxytocin Polymorphism a b s t r a c t Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing 'proof of principle' in a peripheral model that retinoids are potential therapeutic agents in ASD. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. OxytocinClassically, the nonapeptide oxytocin (OT) has been viewed as a hypothalamic neuropeptide that is released into the general circulation from the neural lobe of the pituitary, inducing uterine contractions during parturition and milk ejection during lactation. OT is derived from a pre-prohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary for storage and subsequent release into the bloodstream (see [1] for comprehensive review of the oxytocin receptor system). OT and social behaviorBeyond the long-known peripheral effects of OT, a wealth of animal studies have elaborated the role of OT, or their analogues such as isotocin and vasotocin [2], in molding social behavior from fish to mammals [3]. In the past few years the role of OT has also been examined in our own species, and similar to what has been learned from animal studies, it appears that this nonapeptides also influence social behaviors in humans [4,5]. Indeed, OT has been suggested as the 'great facilitator of life' in a recent review [6].In humans, intranasal administration of OT has been shown to increase trust [7], facilitate mind-reading [8], enhance human memory for social identity [9], increase positive communication between couples [10], increase gaze to the eye region [11] and increase generosity [12]. Intriguingly, OT plasma levels have been linked to individual patterns of maternal-fetal attachment [13] and salivary OT levels were associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms [14]. Social anxiety symptom severity, adjusted for age and gender in a healthy group of subjects, was associated with higher plasma oxytocin levels [15]. Imaging studies reinforce the role of OT in influencing human social ...

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Section: Biomarkers For Autism Spectrum Disordersmentioning

confidence: 99%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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“…The first one was the immediate 5HT precursor, which elevated 5HT levels without acting that genes which regulate 5HT metabolism should be considered as potential candidates in 5HT-related behavioral disorders. Indeed, our findings in autistic subjects indicated that disrupted 5HT homeostasis is related to alterations in 5HT metabolism rather than 5HT uptake [45,46]. Second, the developmental disbalance induced in both 5HT-compartments …”

Section: The Effects Of Pharmacological Treatments On the Expression mentioning

confidence: 63%

Expression of 5HT-related genes after perinatal treatment with 5HT agonists

Blažević

Hranilović

2013

Translational Neuroscience

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Serotonin (5HT) is a biologically active amine with diverse roles in the mammalian organism. Developmental alterations in 5HT homeostasis could lead to exposure of the developing brain to non-optimal serotonin concentrations that may result in developmental and behavioral deficits. In order to explore the molecular basis of the effects of developmental disturbances on 5HT metabolism on adult central 5HT homeostasis, observed in our previous studies, we measured changes in gene expression of the neuronal 5HT-regulating proteins in adult animals after perinatal treatment with the immediate 5HT precursor 5-hydroxytryptophan (5HTP, 25 mg/kg), or monoamine oxidase (MAO) inhibitor tranylcypromine (TCP 2 mg/kg), during the period of the most intensive development of 5HT neurons -from gestational day 12 until postnatal day 21. Adult animals were sacrificed and the relative mRNA levels for tryptophan hydroxylase 2, MAO A, MAO B, receptors 5HT 1A and 5HT 2A , 5HT transporter (5HTT) and vesicular monoamine transporter (VMAT) were determined in the raphe nuclei region and prefrontal cortex using Real-Time Relative qRT-PCR. In comparison to the saline treated animals, treatment with 5HTP caused mild but significant increase in MAO A and MAO B mRNA abundance. TCP-treated animals, besides an increase in mRNA abundance for both MAO genes, displayed significantly increased 5HTT and VMAT2 mRNA levels and significantly decreased 5HT 1A receptor mRNA levels. Our results suggest that perinatal exposure of rats to 5HTP, and especially TCP, induces long-lasting/permanent changes in the expression of 5HT-regulating genes, that presumably underlie 5HT-related neurochemical and behavioral changes in adult animals.

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“…Blood 5-HT concentrations are regulated by the activity of peripheral 5-HT-associated proteins. It is suggested that an increased velocity of kinetics of MAO-B might be an answer to high 5-HT concentrations in the platelets [102,103]. The hyperserotonemia in platelets in autism could be due to an increased uptake of 5-HT into the platelet.…”

Section: Neuropsychiatric Disorders and Serotoninmentioning

confidence: 99%

Serotonin in Neurological Diseases

Dorszewska¹,

Florczak-Wyspiańska²,

Kowalska³

et al. 2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

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Serotonin (5-HT) is responsible for anxiety, aggression, and stress. Alterations in a serotonergic system play a significant role in pathogenesis of neurological diseases and neuropsychiatric disorders. A wide range of disturbances associated with serotonergic neurotransmission results from different functions of 5-HT in a nervous system. It is believed that 5-HT may be involved in the pathogenesis of migraine, epilepsy, Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). In these diseases, disturbances of 5-HT and its metabolites, such as 5-hydroxyindoleacetic acid (5-HIAA), were observed in the plasma, blood platelets, and cerebrospinal fluid (CSF). Changes in the level of this biogenic amine (5-HT) may be associated with malfunction of 5-HT receptors, reuptake transporter for 5-HT (5-HTT, SERT), the enzymes responsible for the synthesis and metabolism of 5-HT, and genetic variants for serotonergic system. It seems that 5-HT and its metabolites may be used as a diagnostic and prognostic marker for neurological diseases or a target for more efficient therapy in neurology in the future.

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Hyperserotonemia in autism: activity of 5HT-associated platelet proteins

Cited by 46 publications

References 58 publications

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Expression of 5HT-related genes after perinatal treatment with 5HT agonists

Serotonin in Neurological Diseases

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