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Papers by Lipa Čičin-Šain
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ranija istraživanja pokazala su da je agresivnost povezana sa serotonergickim parametrima u klini... more Ranija istraživanja pokazala su da je agresivnost povezana sa serotonergickim parametrima u klinickim populacijama. Cilj istraživanja bio je utvrditi da li postoji povezanost između agresivnog ponasanja ispitanika tokom hospitalizacije i serotonergickih parametara, u bolesnika sa posttraumatskim stresnim poremecajem. U ispitivanju je sudjelovalo 40 muskih ispitanika koji su zadovoljili kriterije za postavljanje dijagnoze posttraumatskog stresnog poremecaja, prema DSM - IV klasifikaciji. Agresivnost je procjenjivana na ocjenskoj ljestvici od tri stupnja, a procjenu je vrsio psihijatar. Kao pokazatelji serotonergickog sustava mjereni su razina trombocitnog serotonina , razina aktivnog unosa serotonina u trombocite i aktivnost monoamino oksidaze u trombocitima.
International Journal of Molecular Sciences, Jan 21, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Frontiers in Neuroscience, Mar 25, 2020
Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert op... more 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
Acta Neurobiologiae Experimentalis, 2009
Obesity increases the risk of developing hypertension. Since both pathological entities constitut... more Obesity increases the risk of developing hypertension. Since both pathological entities constitute public health problems, the aim of this study was to investigate RNA expression of adiponectin, leptin and their receptors in adipose tissue in women with class 3 obesity, with or without hypertension. Serum concentrations of these adipokines were also quantitated. Women with obesity and hypertension (n=22) and with obesity without hypertension (n=37) were included. All patients presented class 3 obesity, without diabetes mellitus. The expression of mRNA in: adiponectin, ADIPOR1 and ADIPOR2 was analyzed in visceral (VAT) and subcutaneous (SAT) adipose tissue; leptin and its receptor were only analyzed in SAT, by reverse transcription quantitative PCR. Measurements of adiponectin and leptin concentrations were performed using enzyme-linked immunosorbent assay kits. Analysis of mRNA expressions in VAT and SAT are presented as median and quartiles. Analysis of serum concentrations of adipokines are presented as median and percentiles 25 th-75 th. Women presenting a higher mean arterial pressure, had significantly higher levels of mRNA expression of adiponectin in SAT. Besides, we found several significant positive correlations of these adipokines and their receptors. In conclusion, we found that those women with a higher mean arterial pressure and receiving antihypertensive treatment, presented higher levels of mRNA expression of adiponectin in SAT.
Cambridge University Press eBooks, Mar 4, 2010
By selective breeding for the extreme values of platelet serotonin level (PSL) two sublines of ra... more By selective breeding for the extreme values of platelet serotonin level (PSL) two sublines of rats with constitutional hyperserotonemia/ hyposerotonemia were developed. The velocity of platelet serotonin uptake (PSU), the main determinant of PSL, was used as a further, more specific selection criterion. Directed breeding for its extremes resulted in two sublines of rats with constitutional upregulation/downregulation of platelet 5HT transporter activity, and showed consequent alterations of entire 5HT homeostasis. These sublines, termed Wistar–Zagreb 5HT (WZ-5HT) rats, constitute a genetic rodent model described in this chapter. Besides changes in peripheral 5HT homeostasis, high-5HT and low-5HT sublines of WZ-5HT rats also demonstrate changes in central serotonergic mechanisms. Under physiological conditions, neurochemical differences in the 5HT system between sublines were almost undetectable, but they became evident upon specific pharmacologic challenge, as shown by brain microdialysis study. Differential behavioral phenotypes of 5HT sublines in response to various environmental challenges provide further evidence for differences in their brain functioning. Thus, high-5HT rats exhibit enhanced anxiety-like behaviors while depressive-like behavior and higher alcohol intake co-occur in low-5HT animals. Observed functional and behavioural differences between sublines of WZ-5HT rats strongly indicate that brain serotonergic activity was increased in animals from the high-5HT subline as compared to low-5HT rats. The WZ-5HT rat model may represent an integrative model for serotonin and serotonin transporter research, Experimental Models of Serotonin Transporter Research, eds. A. V. Kalueff and J. L. LaPorte. Published by Cambridge University Press. # A. V. Kalueff and J. L. LaPorte 2009. 214 Comp. by: kkavitha Stage : Proof ChapterID: 9780521514873c07 Date:3/4/ 09 Time🔞55:17 Filepath:H:/01_CUP/3B2/Kalueff9780521514873/ Applications/3B2/Proof/9780521514873c07.3d incorporating changes at the genomic/genetic and phenotypic (neurodevelopmental, structural, biochemical, behavioral, etc.) levels and encompassing both central and peripheral 5HT functioning.
Neuropeptides, Oct 1, 2013
Due to their involvement in dependence pathways, opioid system genes represent strong candidates ... more Due to their involvement in dependence pathways, opioid system genes represent strong candidates for association studies investigating alcoholism. In this study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa (OPRK1) opioid receptors and precursors of their ligands - proopiomelanocortin (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins, were analyzed in a case-control study that included 354 male alcohol-dependent and 357 male control subjects from Croatian population. Analysis of allele and genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN revealed no differences between the tested groups. The same was true when alcohol-dependent persons were subdivided according to the Cloninger's criteria into type-1 and type-2 groups, known to differ in the extent of genetic control. Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.
International Journal of Molecular Sciences
Maintaining energy balance is a complex physiological function whose dysregulation can lead to ob... more Maintaining energy balance is a complex physiological function whose dysregulation can lead to obesity and associated metabolic disorders. The bioamine serotonin (5HT) is an important regulator of energy homeostasis, with its central and peripheral pools influencing energy status in opposing ways. Using sublines of rats with constitutionally increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, we have previously shown that under standard diet constitutionally higher 5HT activity is associated with increased body weight, adiposity, and impaired glucose homeostasis. Here, we investigated the response of 5HT sublines to an obesogenic diet. Consistent with previous findings, high-5HT animals fed a standard diet had poorer metabolic health. However, in response to a high-fat diet, only low-5HT animals increased body weight and insulin resistance. They also showed more pronounced changes in blood metabolic parameters and the expression of various metabolic genes in hypothalamu...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ranija istraživanja pokazala su da je agresivnost povezana sa serotonergickim parametrima u klini... more Ranija istraživanja pokazala su da je agresivnost povezana sa serotonergickim parametrima u klinickim populacijama. Cilj istraživanja bio je utvrditi da li postoji povezanost između agresivnog ponasanja ispitanika tokom hospitalizacije i serotonergickih parametara, u bolesnika sa posttraumatskim stresnim poremecajem. U ispitivanju je sudjelovalo 40 muskih ispitanika koji su zadovoljili kriterije za postavljanje dijagnoze posttraumatskog stresnog poremecaja, prema DSM - IV klasifikaciji. Agresivnost je procjenjivana na ocjenskoj ljestvici od tri stupnja, a procjenu je vrsio psihijatar. Kao pokazatelji serotonergickog sustava mjereni su razina trombocitnog serotonina , razina aktivnog unosa serotonina u trombocite i aktivnost monoamino oksidaze u trombocitima.
International Journal of Molecular Sciences, Jan 21, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Frontiers in Neuroscience, Mar 25, 2020
Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert op... more 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
Acta Neurobiologiae Experimentalis, 2009
Obesity increases the risk of developing hypertension. Since both pathological entities constitut... more Obesity increases the risk of developing hypertension. Since both pathological entities constitute public health problems, the aim of this study was to investigate RNA expression of adiponectin, leptin and their receptors in adipose tissue in women with class 3 obesity, with or without hypertension. Serum concentrations of these adipokines were also quantitated. Women with obesity and hypertension (n=22) and with obesity without hypertension (n=37) were included. All patients presented class 3 obesity, without diabetes mellitus. The expression of mRNA in: adiponectin, ADIPOR1 and ADIPOR2 was analyzed in visceral (VAT) and subcutaneous (SAT) adipose tissue; leptin and its receptor were only analyzed in SAT, by reverse transcription quantitative PCR. Measurements of adiponectin and leptin concentrations were performed using enzyme-linked immunosorbent assay kits. Analysis of mRNA expressions in VAT and SAT are presented as median and quartiles. Analysis of serum concentrations of adipokines are presented as median and percentiles 25 th-75 th. Women presenting a higher mean arterial pressure, had significantly higher levels of mRNA expression of adiponectin in SAT. Besides, we found several significant positive correlations of these adipokines and their receptors. In conclusion, we found that those women with a higher mean arterial pressure and receiving antihypertensive treatment, presented higher levels of mRNA expression of adiponectin in SAT.
Cambridge University Press eBooks, Mar 4, 2010
By selective breeding for the extreme values of platelet serotonin level (PSL) two sublines of ra... more By selective breeding for the extreme values of platelet serotonin level (PSL) two sublines of rats with constitutional hyperserotonemia/ hyposerotonemia were developed. The velocity of platelet serotonin uptake (PSU), the main determinant of PSL, was used as a further, more specific selection criterion. Directed breeding for its extremes resulted in two sublines of rats with constitutional upregulation/downregulation of platelet 5HT transporter activity, and showed consequent alterations of entire 5HT homeostasis. These sublines, termed Wistar–Zagreb 5HT (WZ-5HT) rats, constitute a genetic rodent model described in this chapter. Besides changes in peripheral 5HT homeostasis, high-5HT and low-5HT sublines of WZ-5HT rats also demonstrate changes in central serotonergic mechanisms. Under physiological conditions, neurochemical differences in the 5HT system between sublines were almost undetectable, but they became evident upon specific pharmacologic challenge, as shown by brain microdialysis study. Differential behavioral phenotypes of 5HT sublines in response to various environmental challenges provide further evidence for differences in their brain functioning. Thus, high-5HT rats exhibit enhanced anxiety-like behaviors while depressive-like behavior and higher alcohol intake co-occur in low-5HT animals. Observed functional and behavioural differences between sublines of WZ-5HT rats strongly indicate that brain serotonergic activity was increased in animals from the high-5HT subline as compared to low-5HT rats. The WZ-5HT rat model may represent an integrative model for serotonin and serotonin transporter research, Experimental Models of Serotonin Transporter Research, eds. A. V. Kalueff and J. L. LaPorte. Published by Cambridge University Press. # A. V. Kalueff and J. L. LaPorte 2009. 214 Comp. by: kkavitha Stage : Proof ChapterID: 9780521514873c07 Date:3/4/ 09 Time🔞55:17 Filepath:H:/01_CUP/3B2/Kalueff9780521514873/ Applications/3B2/Proof/9780521514873c07.3d incorporating changes at the genomic/genetic and phenotypic (neurodevelopmental, structural, biochemical, behavioral, etc.) levels and encompassing both central and peripheral 5HT functioning.
Neuropeptides, Oct 1, 2013
Due to their involvement in dependence pathways, opioid system genes represent strong candidates ... more Due to their involvement in dependence pathways, opioid system genes represent strong candidates for association studies investigating alcoholism. In this study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa (OPRK1) opioid receptors and precursors of their ligands - proopiomelanocortin (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins, were analyzed in a case-control study that included 354 male alcohol-dependent and 357 male control subjects from Croatian population. Analysis of allele and genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN revealed no differences between the tested groups. The same was true when alcohol-dependent persons were subdivided according to the Cloninger's criteria into type-1 and type-2 groups, known to differ in the extent of genetic control. Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.
International Journal of Molecular Sciences
Maintaining energy balance is a complex physiological function whose dysregulation can lead to ob... more Maintaining energy balance is a complex physiological function whose dysregulation can lead to obesity and associated metabolic disorders. The bioamine serotonin (5HT) is an important regulator of energy homeostasis, with its central and peripheral pools influencing energy status in opposing ways. Using sublines of rats with constitutionally increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, we have previously shown that under standard diet constitutionally higher 5HT activity is associated with increased body weight, adiposity, and impaired glucose homeostasis. Here, we investigated the response of 5HT sublines to an obesogenic diet. Consistent with previous findings, high-5HT animals fed a standard diet had poorer metabolic health. However, in response to a high-fat diet, only low-5HT animals increased body weight and insulin resistance. They also showed more pronounced changes in blood metabolic parameters and the expression of various metabolic genes in hypothalamu...