PMC:3852299 / 7698-12098 JSONTXT

{"project":"NEUROSES","denotations":[{"id":"T256","span":{"begin":588,"end":591},"obj":"PATO_0000011"},{"id":"T257","span":{"begin":588,"end":591},"obj":"CHEBI_84123"},{"id":"T258","span":{"begin":626,"end":634},"obj":"PATO_0001688"},{"id":"T259","span":{"begin":691,"end":696},"obj":"PATO_0000694"},{"id":"T260","span":{"begin":1058,"end":1067},"obj":"CHEBI_63534"},{"id":"T261","span":{"begin":1058,"end":1067},"obj":"CHEBI_25375"},{"id":"T262","span":{"begin":1085,"end":1095},"obj":"CHEBI_25212"},{"id":"T263","span":{"begin":1117,"end":1121},"obj":"CHEBI_37527"},{"id":"T264","span":{"begin":1123,"end":1129},"obj":"CHEBI_27823"},{"id":"T265","span":{"begin":1232,"end":1239},"obj":"PATO_0000184"},{"id":"T266","span":{"begin":1256,"end":1267},"obj":"PATO_0000085"},{"id":"T267","span":{"begin":1290,"end":1297},"obj":"CHEBI_24621"},{"id":"T268","span":{"begin":1465,"end":1473},"obj":"CHEBI_36080"},{"id":"T269","span":{"begin":1478,"end":1487},"obj":"PATO_0000627"},{"id":"T270","span":{"begin":1566,"end":1573},"obj":"PATO_0000392"},{"id":"T271","span":{"begin":1790,"end":1799},"obj":"CHEBI_350546"},{"id":"T272","span":{"begin":1919,"end":1928},"obj":"CHEBI_350546"},{"id":"T273","span":{"begin":2046,"end":2055},"obj":"CHEBI_350546"},{"id":"T274","span":{"begin":2189,"end":2198},"obj":"CHEBI_350546"},{"id":"T275","span":{"begin":2299,"end":2308},"obj":"CHEBI_350546"},{"id":"T276","span":{"begin":2383,"end":2392},"obj":"CHEBI_350546"},{"id":"T277","span":{"begin":2443,"end":2452},"obj":"CHEBI_350546"},{"id":"T278","span":{"begin":2647,"end":2656},"obj":"CHEBI_350546"},{"id":"T279","span":{"begin":2748,"end":2757},"obj":"CHEBI_350546"},{"id":"T280","span":{"begin":2804,"end":2813},"obj":"CHEBI_350546"},{"id":"T281","span":{"begin":2925,"end":2934},"obj":"CHEBI_350546"},{"id":"T282","span":{"begin":1790,"end":1799},"obj":"CHEBI_28790"},{"id":"T283","span":{"begin":1919,"end":1928},"obj":"CHEBI_28790"},{"id":"T284","span":{"begin":2046,"end":2055},"obj":"CHEBI_28790"},{"id":"T285","span":{"begin":2189,"end":2198},"obj":"CHEBI_28790"},{"id":"T286","span":{"begin":2299,"end":2308},"obj":"CHEBI_28790"},{"id":"T287","span":{"begin":2383,"end":2392},"obj":"CHEBI_28790"},{"id":"T288","span":{"begin":2443,"end":2452},"obj":"CHEBI_28790"},{"id":"T289","span":{"begin":2647,"end":2656},"obj":"CHEBI_28790"},{"id":"T290","span":{"begin":2748,"end":2757},"obj":"CHEBI_28790"},{"id":"T291","span":{"begin":2804,"end":2813},"obj":"CHEBI_28790"},{"id":"T292","span":{"begin":2925,"end":2934},"obj":"CHEBI_28790"},{"id":"T293","span":{"begin":1905,"end":1911},"obj":"PATO_0000461"},{"id":"T294","span":{"begin":2002,"end":2012},"obj":"PATO_0002107"},{"id":"T295","span":{"begin":2062,"end":2066},"obj":"PATO_0001026"},{"id":"T296","span":{"begin":2130,"end":2139},"obj":"CHEBI_63534"},{"id":"T297","span":{"begin":2130,"end":2139},"obj":"CHEBI_25375"},{"id":"T298","span":{"begin":2235,"end":2243},"obj":"CHEBI_36080"},{"id":"T299","span":{"begin":2552,"end":2560},"obj":"CHEBI_36080"},{"id":"T300","span":{"begin":2422,"end":2426},"obj":"CHEBI_50906"},{"id":"T301","span":{"begin":2528,"end":2536},"obj":"PATO_0002331"},{"id":"T302","span":{"begin":2537,"end":2542},"obj":"CHEBI_30216"},{"id":"T303","span":{"begin":2537,"end":2542},"obj":"PATO_0001344"},{"id":"T304","span":{"begin":2543,"end":2551},"obj":"PATO_0001759"},{"id":"T305","span":{"begin":2619,"end":2627},"obj":"PATO_0000460"},{"id":"T306","span":{"begin":2723,"end":2730},"obj":"PATO_0000498"},{"id":"T307","span":{"begin":2723,"end":2730},"obj":"PATO_0001863"},{"id":"T308","span":{"begin":2767,"end":2777},"obj":"CHEBI_35222"},{"id":"T309","span":{"begin":2814,"end":2821},"obj":"PATO_0000025"},{"id":"T310","span":{"begin":3091,"end":3099},"obj":"PATO_0000070"},{"id":"T311","span":{"begin":3165,"end":3169},"obj":"CHEBI_50906"},{"id":"T312","span":{"begin":3240,"end":3244},"obj":"CHEBI_50906"},{"id":"T313","span":{"begin":3173,"end":3182},"obj":"CHEBI_350546"},{"id":"T314","span":{"begin":3219,"end":3228},"obj":"CHEBI_350546"},{"id":"T315","span":{"begin":3331,"end":3340},"obj":"CHEBI_350546"},{"id":"T316","span":{"begin":3658,"end":3667},"obj":"CHEBI_350546"},{"id":"T317","span":{"begin":3849,"end":3858},"obj":"CHEBI_350546"},{"id":"T318","span":{"begin":3989,"end":3998},"obj":"CHEBI_350546"},{"id":"T319","span":{"begin":4129,"end":4138},"obj":"CHEBI_350546"},{"id":"T320","span":{"begin":3173,"end":3182},"obj":"CHEBI_28790"},{"id":"T321","span":{"begin":3219,"end":3228},"obj":"CHEBI_28790"},{"id":"T322","span":{"begin":3331,"end":3340},"obj":"CHEBI_28790"},{"id":"T323","span":{"begin":3658,"end":3667},"obj":"CHEBI_28790"},{"id":"T324","span":{"begin":3849,"end":3858},"obj":"CHEBI_28790"},{"id":"T325","span":{"begin":3989,"end":3998},"obj":"CHEBI_28790"},{"id":"T326","span":{"begin":4129,"end":4138},"obj":"CHEBI_28790"},{"id":"T327","span":{"begin":3195,"end":3203},"obj":"PATO_0000173"},{"id":"T328","span":{"begin":3258,"end":3266},"obj":"PATO_0000173"},{"id":"T329","span":{"begin":3685,"end":3689},"obj":"CHEBI_37527"},{"id":"T330","span":{"begin":4089,"end":4096},"obj":"CHEBI_5931"},{"id":"T331","span":{"begin":4107,"end":4114},"obj":"CHEBI_5931"},{"id":"T332","span":{"begin":4169,"end":4172},"obj":"CHEBI_29447"},{"id":"T333","span":{"begin":4169,"end":4172},"obj":"CHEBI_29426"},{"id":"T334","span":{"begin":4169,"end":4172},"obj":"CHEBI_29441"},{"id":"T335","span":{"begin":4169,"end":4172},"obj":"CHEBI_18022"},{"id":"T336","span":{"begin":4169,"end":4172},"obj":"CHEBI_29425"},{"id":"T213","span":{"begin":25,"end":34},"obj":"CHEBI_350546"},{"id":"T214","span":{"begin":57,"end":66},"obj":"CHEBI_350546"},{"id":"T215","span":{"begin":95,"end":104},"obj":"CHEBI_350546"},{"id":"T216","span":{"begin":286,"end":295},"obj":"CHEBI_350546"},{"id":"T217","span":{"begin":302,"end":311},"obj":"CHEBI_350546"},{"id":"T218","span":{"begin":644,"end":653},"obj":"CHEBI_350546"},{"id":"T219","span":{"begin":787,"end":796},"obj":"CHEBI_350546"},{"id":"T220","span":{"begin":936,"end":945},"obj":"CHEBI_350546"},{"id":"T221","span":{"begin":1005,"end":1014},"obj":"CHEBI_350546"},{"id":"T222","span":{"begin":1159,"end":1168},"obj":"CHEBI_350546"},{"id":"T223","span":{"begin":1369,"end":1378},"obj":"CHEBI_350546"},{"id":"T224","span":{"begin":95,"end":104},"obj":"CHEBI_28790"},{"id":"T225","span":{"begin":286,"end":295},"obj":"CHEBI_28790"},{"id":"T226","span":{"begin":302,"end":311},"obj":"CHEBI_28790"},{"id":"T227","span":{"begin":644,"end":653},"obj":"CHEBI_28790"},{"id":"T228","span":{"begin":787,"end":796},"obj":"CHEBI_28790"},{"id":"T229","span":{"begin":936,"end":945},"obj":"CHEBI_28790"},{"id":"T230","span":{"begin":1005,"end":1014},"obj":"CHEBI_28790"},{"id":"T231","span":{"begin":1159,"end":1168},"obj":"CHEBI_28790"},{"id":"T232","span":{"begin":1369,"end":1378},"obj":"CHEBI_28790"},{"id":"T233","span":{"begin":43,"end":53},"obj":"PATO_0000076"},{"id":"T234","span":{"begin":150,"end":162},"obj":"CHEBI_57912"},{"id":"T235","span":{"begin":164,"end":176},"obj":"CHEBI_57912"},{"id":"T236","span":{"begin":150,"end":162},"obj":"CHEBI_16828"},{"id":"T237","span":{"begin":164,"end":176},"obj":"CHEBI_16828"},{"id":"T238","span":{"begin":150,"end":162},"obj":"CHEBI_29954"},{"id":"T239","span":{"begin":164,"end":176},"obj":"CHEBI_29954"},{"id":"T240","span":{"begin":196,"end":215},"obj":"CHEBI_28171"},{"id":"T241","span":{"begin":217,"end":222},"obj":"CHEBI_28171"},{"id":"T242","span":{"begin":380,"end":386},"obj":"PATO_0001701"},{"id":"T243","span":{"begin":410,"end":426},"obj":"CHEBI_25512"},{"id":"T244","span":{"begin":1340,"end":1356},"obj":"CHEBI_25512"},{"id":"T245","span":{"begin":456,"end":459},"obj":"CHEBI_29447"},{"id":"T246","span":{"begin":1364,"end":1367},"obj":"CHEBI_29447"},{"id":"T247","span":{"begin":456,"end":459},"obj":"CHEBI_29426"},{"id":"T248","span":{"begin":1364,"end":1367},"obj":"CHEBI_29426"},{"id":"T249","span":{"begin":456,"end":459},"obj":"CHEBI_29441"},{"id":"T250","span":{"begin":1364,"end":1367},"obj":"CHEBI_29441"},{"id":"T251","span":{"begin":456,"end":459},"obj":"CHEBI_18022"},{"id":"T252","span":{"begin":1364,"end":1367},"obj":"CHEBI_18022"},{"id":"T253","span":{"begin":456,"end":459},"obj":"CHEBI_29425"},{"id":"T254","span":{"begin":1364,"end":1367},"obj":"CHEBI_29425"},{"id":"T255","span":{"begin":530,"end":540},"obj":"PATO_0001510"}],"text":"Physiological actions of serotonin and its regulation by serotonin reuptake transporter (SERT)\nSerotonin is synthesised from the essential amino acid L-tryptophan. L-tryptophan is hydroxylated to 5-hydroxytryptophan (5-HTP) then decarboxylated by aromatic-L-amino acid decarboxylase to serotonin [38]. Serotonin produced peripherally does not cross the blood-brain barrier of the mature brain and as such, the neurotransmitter has to be synthesized in the CNS. It must be noted, however, that the blood brain barrier is not fully functional in the developing human brain until 2 years of age and it has been hypothesized that elevated platelet serotonin may alter the monamine levels during early brain development in autistic children [39]. After its release from serotonergic neurons, serotonin will bind its receptors at the synaptic site to activate intracellular signalling pathways to induce physiological effects. The actions of serotonin are then terminated when it is rapidly taken up by a SERT. Serotonin is catabolised by the mitochondrial enzyme monoamine oxidase A to its metabolite 5-hydroxyindolacetic acid (5-HIAA).\nThe behavioural effects of serotonin are numerous as it regulates mood, appetite, body temperature, arousal, moderates pain sensitivity, sexual behaviour and hormone release [14]. Other than its actions as a neurotransmitter in the CNS, serotonin is released in the periphery to mediate a range of physiological activities. The SERT proteins are localised to the presynaptic terminals of the serotonergic neurons [40] and is found in limited places such as the specialised cells of the gut [41], placenta [42], lung [43], pancreas [44] and adrenal chromaffin cells [45], blood lymphocytes [41] and platelets [46]. In the periphery, tissues take up and store serotonin in vesicles where it is released in response to local stimuli [47]. The importance of SERT in regulating normal tissue serotonin levels was demonstrated in SERT-deficient mice, where platelets and most peripheral organs were found to be empty of serotonin. This work showed that there are no compensatory mechanisms such as other monoamine transport systems that could re-establish tissue serotonin levels [47]. Platelets express SERT proteins that are identical to brain SERT [48] and they acquire serotonin released by the enterochromaffin cells as they circulate through the gut. Serotonin captured by platelets have a role in injury where serotonin release can alter blood flow [49] as well as stimulating the production of adhesive alpha-granular proteins in activated platelets [50], and as indicated previously, abnormal levels of platelet serotonin have been observed in ASD-diagnosed children and their relatives. Chronic use of selective serotonin reuptake inhibitors (SSRIs) decrease platelet serotonin content, protects against myocardial infarction or intensifies bleeding episodes [51,52]. Subsequently, excess serotonin uptake may contribute to platelet hyperactivity and thrombosis as reported, with an association of SERT polymorphisms with cardiovascular disease [53]. The presence of SERT proteins on the placental brush border membrane, and the role of serotonin in vascular function indicates that serotonin may have a role in placental function and therefore, growth and development of the human foetus [42]. Serotonin is synthesized by enteric neurons and enterochromaffin cells of the gut where it locally regulates digestive processes [54,55]. It can be released into the blood or into the lumen of the gut where it can modify intestinal transport, proliferation of gastrointestinal epithelium and modulation of intestinal motility. Serotonin inhibits gastric acid secretion and may be an endogenous enterogastrone, and stimulates the production and release of gastric and colonic mucus [56]. In the gastrointestinal tract, serotonin acts as a crucial signalling molecule initiating responses such as nausea, vomiting, and peristaltic and secretory reflexes [57]. Serotonin is taken up into the β-cells of the pancreas, where it is stored in granules that contain insulin to modify insulin release [44].\nSerotonin has specific functions in the CNS and in the periphery where it regulates many physiological activities. Problems in serotonergic signalling in some of these systems have been implicated as comorbidities that occur with ASD as discussed in the previous section."}

{"project":"2_test","denotations":[{"id":"24103554-24178430-70233130","span":{"begin":297,"end":299},"obj":"24178430"},{"id":"24103554-15730889-70233131","span":{"begin":737,"end":739},"obj":"15730889"},{"id":"24103554-16002261-70233132","span":{"begin":1307,"end":1309},"obj":"16002261"},{"id":"24103554-7869097-70233133","span":{"begin":1546,"end":1548},"obj":"7869097"},{"id":"24103554-12909457-70233134","span":{"begin":1623,"end":1625},"obj":"12909457"},{"id":"24103554-2914900-70233135","span":{"begin":1638,"end":1640},"obj":"2914900"},{"id":"24103554-8935709-70233136","span":{"begin":1649,"end":1651},"obj":"8935709"},{"id":"24103554-19859528-70233137","span":{"begin":1664,"end":1666},"obj":"19859528"},{"id":"24103554-9245500-70233138","span":{"begin":1698,"end":1700},"obj":"9245500"},{"id":"24103554-12909457-70233139","span":{"begin":1722,"end":1724},"obj":"12909457"},{"id":"24103554-18317590-70233140","span":{"begin":1741,"end":1743},"obj":"18317590"},{"id":"24103554-18824000-70233141","span":{"begin":1863,"end":1865},"obj":"18824000"},{"id":"24103554-18824000-70233142","span":{"begin":2207,"end":2209},"obj":"18824000"},{"id":"24103554-7684072-70233143","span":{"begin":2278,"end":2280},"obj":"7684072"},{"id":"24103554-2939211-70233144","span":{"begin":2483,"end":2485},"obj":"2939211"},{"id":"24103554-14697203-70233145","span":{"begin":2585,"end":2587},"obj":"14697203"},{"id":"24103554-12821544-70233146","span":{"begin":2896,"end":2898},"obj":"12821544"},{"id":"24103554-15953802-70233147","span":{"begin":2899,"end":2901},"obj":"15953802"},{"id":"24103554-16209960-70233148","span":{"begin":3082,"end":3084},"obj":"16209960"},{"id":"24103554-2914900-70233149","span":{"begin":3326,"end":3328},"obj":"2914900"},{"id":"24103554-331327-70233150","span":{"begin":3461,"end":3463},"obj":"331327"},{"id":"24103554-3919396-70233151","span":{"begin":3813,"end":3815},"obj":"3919396"},{"id":"24103554-16750380-70233152","span":{"begin":3984,"end":3986},"obj":"16750380"},{"id":"24103554-19859528-70233153","span":{"begin":4124,"end":4126},"obj":"19859528"}],"text":"Physiological actions of serotonin and its regulation by serotonin reuptake transporter (SERT)\nSerotonin is synthesised from the essential amino acid L-tryptophan. L-tryptophan is hydroxylated to 5-hydroxytryptophan (5-HTP) then decarboxylated by aromatic-L-amino acid decarboxylase to serotonin [38]. Serotonin produced peripherally does not cross the blood-brain barrier of the mature brain and as such, the neurotransmitter has to be synthesized in the CNS. It must be noted, however, that the blood brain barrier is not fully functional in the developing human brain until 2 years of age and it has been hypothesized that elevated platelet serotonin may alter the monamine levels during early brain development in autistic children [39]. After its release from serotonergic neurons, serotonin will bind its receptors at the synaptic site to activate intracellular signalling pathways to induce physiological effects. The actions of serotonin are then terminated when it is rapidly taken up by a SERT. Serotonin is catabolised by the mitochondrial enzyme monoamine oxidase A to its metabolite 5-hydroxyindolacetic acid (5-HIAA).\nThe behavioural effects of serotonin are numerous as it regulates mood, appetite, body temperature, arousal, moderates pain sensitivity, sexual behaviour and hormone release [14]. Other than its actions as a neurotransmitter in the CNS, serotonin is released in the periphery to mediate a range of physiological activities. The SERT proteins are localised to the presynaptic terminals of the serotonergic neurons [40] and is found in limited places such as the specialised cells of the gut [41], placenta [42], lung [43], pancreas [44] and adrenal chromaffin cells [45], blood lymphocytes [41] and platelets [46]. In the periphery, tissues take up and store serotonin in vesicles where it is released in response to local stimuli [47]. The importance of SERT in regulating normal tissue serotonin levels was demonstrated in SERT-deficient mice, where platelets and most peripheral organs were found to be empty of serotonin. This work showed that there are no compensatory mechanisms such as other monoamine transport systems that could re-establish tissue serotonin levels [47]. Platelets express SERT proteins that are identical to brain SERT [48] and they acquire serotonin released by the enterochromaffin cells as they circulate through the gut. Serotonin captured by platelets have a role in injury where serotonin release can alter blood flow [49] as well as stimulating the production of adhesive alpha-granular proteins in activated platelets [50], and as indicated previously, abnormal levels of platelet serotonin have been observed in ASD-diagnosed children and their relatives. Chronic use of selective serotonin reuptake inhibitors (SSRIs) decrease platelet serotonin content, protects against myocardial infarction or intensifies bleeding episodes [51,52]. Subsequently, excess serotonin uptake may contribute to platelet hyperactivity and thrombosis as reported, with an association of SERT polymorphisms with cardiovascular disease [53]. The presence of SERT proteins on the placental brush border membrane, and the role of serotonin in vascular function indicates that serotonin may have a role in placental function and therefore, growth and development of the human foetus [42]. Serotonin is synthesized by enteric neurons and enterochromaffin cells of the gut where it locally regulates digestive processes [54,55]. It can be released into the blood or into the lumen of the gut where it can modify intestinal transport, proliferation of gastrointestinal epithelium and modulation of intestinal motility. Serotonin inhibits gastric acid secretion and may be an endogenous enterogastrone, and stimulates the production and release of gastric and colonic mucus [56]. In the gastrointestinal tract, serotonin acts as a crucial signalling molecule initiating responses such as nausea, vomiting, and peristaltic and secretory reflexes [57]. Serotonin is taken up into the β-cells of the pancreas, where it is stored in granules that contain insulin to modify insulin release [44].\nSerotonin has specific functions in the CNS and in the periphery where it regulates many physiological activities. Problems in serotonergic signalling in some of these systems have been implicated as comorbidities that occur with ASD as discussed in the previous section."}