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Актуальность. По данным разных авторов, метаболический синдром распространен более чем у 50 % больных шизофренией. Одной из причин формирования метаболического синдрома является избыточное содержание в крови неэстерифицированных жирных кислот (НЭЖК). Известно, что антипсихотическая терапия у больных шизофренией сопряжена с увеличением количества НЭЖК в сыворотке крови. Дофамин-бета-гидроксилаза (DβH) – фермент, участвующий в обмене дофамина и норадреналина. Некоторые полиморфные варианты гена DβH ассоциированы с такими метаболическими нарушениями, как ожирение и сахарный диабет 25го типа. Цель исследования – изучение ассоциации между полиморфным вариантом гена дофамин-β-гидроксилазы (DβH) rs1611115 и содержанием неэстерифицированных жирных кислот у больных с первым эпизодом параноидной шизофрении при терапии галоперидолом и рисперидоном. Материал и методы. В исследование было включено 212 пациентов (109 больных мужского пола и 103 женского) с диагнозом «шизофрения параноидная, период наблюдения менее года» (F20.09). Возраст пациентов составил 27 ± 6 лет. В группу контроля вошли 132 здоровых добровольца. Пациенты и представители контрольной группы были европеоидной расы, родились и проживали на территории Забайкальского края. Они были сопоставимы между собой по полу и возрасту. Геномную ДНК человека выделяли из лейкоцитов цельной крови. Анализ rs1611115 проводили методом полимеразно-цепной реакции с электрофоретической детекцией продуктов. Содержание НЭЖК в сыворотке крови измеряли с использованием колориметрического метода определения медных солей. Уровень глицерола в сыворотке крови выявляли методом ферментативного фотометрического теста с глицерол- 3-фосфатоксидазой. Рассчитывали коэффициент «НЭЖК/глицерол», отражающий степень утилизации жирных кислот. Результаты. У больных с первым эпизодом параноидной шизофрении установлено повышенное содержание НЭЖК в сыворотке крови еще до начала антипсихотической терапии. При этом не обнаружено различий в количестве НЭЖК и свободного глицерола сыворотки крови между носителями генотипов С/С и С/Т + Т/Т. Терапия галоперидолом и рисперидоном сопровождалась повышением концентрации НЭЖК в сыворотке крови. У больных, получавших лечение рисперидоном, на 85й неделе исследования содержание НЭЖК в сыворотке крови не различалось между носителями генотипов С/С и С/Т + Т/Т, в то время как в группе больных, принимавших галоперидол, на 85й неделе терапии концентрация НЭЖК в сыворотке у носителей генотипа С/С была больше, чем у носителей генотипов С/Т + Т/Т. Различное влияние галоперидола и рисперидона на содержание НЭЖК и свободного глицерола в сыворотке крови обнаружено только у носителей генотипа С/С. Заключение. Терапия галоперидолом и рисперидоном у больных с первым эпизодом шизофрении сопровождается увеличением содержания НЭЖК в сыворотке крови. Выраженность этих изменений зависит не только от используемого нейролептика, но и от носительства генотипов rs1611115. Необходимы дальнейшие фармакогенетические исследования по изучению метаболических эффектов антипсихотиков в зависимости от генетических особенностей больных для разработки персонифицированного подхода к терапии.

Background: Patients with schizophrenia are at a higher risk for suicide compared with the general population. Dopamine beta‐hydroxylase (DβH) plays a key role in the conversion of dopamine to norepinephrine, which is related to suicidal behavior and cognitive regulation. Objective: To examine whether there is the effect of DβH 5′‐insertion/deletion (Ins/Del) polymorphism on cognitive performance in suicide attempters with chronic schizophrenia. Methods: This polymorphism was detected in 114 suicide attempters and 617 non‐suicide attempters with chronic schizophrenia. Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results: The allelic and genotypic frequencies of this polymorphism between two groups did not differ after controlling for covariates (both, p >.05). There were no differences in RBANS scores between two groups after adjusting for covariates (all, p >.05). However, based on the genotype grouping in suicide attempters and non‐attempters, the attention score significantly differed after adjusting for covariates (both, p <.05). Further analysis indicated that this polymorphism was associated with attention score in suicide attempters (p <.05), but not in non‐suicide attempters (p >.05). Conclusions: DβH 5′‐Ins/Del polymorphism was not a risk locus of suicide attempters, but it was implicated in attention regulation in suicide attempters with chronic schizophrenia. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation has a strong biological effect on skin biology, and it switches on adaptive mechanisms to maintain homeostasis in organs such as the skin, adrenal glands, and brain. In this study, we examined the adaptation of the body to repeated bouts of UVB radiation, especially with respect to the catecholamine synthesis pathway of the adrenal glands. The effects of UVB on catecholamine-related enzymes were determined by neurochemical and histological analyses. To evaluate catecholamine changes after chronic excessive UVB irradiation of mouse skin, we examined dopamine and norepinephrine levels in the adrenal glands and blood from UV-irradiated and sham-irradiated mice. We found that chronic excessive UVB exposure significantly reduced dopamine levels in both tissues but did not affect norepinephrine levels. In addition, UVB irradiation significantly increased the levels of related enzymes tyrosine hydroxylase and dopamine-β-hydroxylase. Furthermore, we also found that apoptosis-associated markers were increased and that oxidative defense proteins were decreased, which might have contributed to the marked structural abnormalities in the adrenal medullas of the chronically UVB-irradiated mice. This is the first evidence of the damage to the adrenal gland and subsequent dysregulation of catecholamine metabolism induced by chronic exposure to UVB.

Introduction. Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver. Therefore, this study concerns BPA exposure and sympathetic intrahepatic innervation in reference to several neuropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). Materials and methods. Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsules orally with bisphenol at a dose of 0.05 mg/kg b.w./day; a dose of 0.5 mg/kg b.w./day and placebo capsules as a control. After 28 days of oral BPA intake, the animals were euthanized, perfused with 4% paraformaldehyde (PFA), and livers were collected and fixed in PFA. The cryostat sections were subjected to a routine double-labeling immunofluorescence technique. The primary antibodies were directed against dopamine beta hydroxylase (DβH), which is a marker for sympathetic nerves, and one of the investigated neuropeptides: CART, GAL, CGRP and SP, which co-localized the investigated nerves. Immunoreactive nerves were counted in the liver and the percentage presence of each neuronal combination in particular samples of each experimental group were determined and analyzed statistically. Results. The BPA oral intake at low and ten times higher dosage caused an increase of the number of sympathetic nerve fibers within the porcine liver by 48.6% and 63.7%, respectively. Moreover, BPA exposure caused an increased presence of sympathetic nerve fibers in these two experimental groups, which were co-localized with CART and GAL up to 65.9%/173.2% and 147.4%/126.3%, respectively. At the lower BPA doses of 50 µg/kg b.w./day, the percentages of SP+/DβH+ and CGRP+/DβH+ nerve fibers were similar to the control. However at a ten times higher dose, BPA caused an increased number of SP+/ DβH+ and CGRP+/ DβH+ nerve fibers in the liver, up to 46.4% and 73.5% respectively. Conclusions. BPA caused an increase in the number of sympathetic nerve fibers as well as sympathetic nerve fibers which co-localized with neuropeptides in the porcine liver. The increase in CART and GAL were exceptionally high even at low BPA doses. BPA food contamination may dysregulate liver sympathetic innervation, and thereby may change the oxygenated blood supply, alter metabolism and disrupt the activity of hepatic parenchymal cells. [ABSTRACT FROM AUTHOR]

Abstract: Co-expression of dopamine β-hydroxylase (DβH) and neuropeptide Y (NPY) has never been examined in ovary (OV) and umbilical cord (UC) of the European bison (Eb), the endangered wild species. The OV and UC samples were harvested from seasonally eliminated Eb females (45–120 days post coitum). Frozen histological sections were examined by double fluorescent immunohistochemistry (dF-IHC), using the primary mouse anti-DβH monoclonals and rabbit anti-NPY polyclonals and then the immunocomplexes were visualized with FITC and CY3 fluorophores, respectively. Numerous DβH immunoreactive nerve fibers (DβH-IRs) and a little less frequent NPY-IRs were found in the bundle-like structures, innervating mainly perivascular regions of the OV. The NPY-IRs constantly co-expressed DβH, while some DβH-IRs did not express NPY. This specific pattern of innervation was observed both in the stromal and cortical regions of the OV. The simultaneous co-expression of DβH and NPY were also detected in the UC, in which specific single or bundle-like structures ran along the smooth muscles of blood vessels. The spatial-specific co-expression of DβH and NPY in OV and UC, may suggest that these markers are involved in the control of vascularization that regulates nourishing blood circulation required for proper pregnancy maintenance and efficient embryo/fetus development in the Eb. [Copyright &y& Elsevier]

Early onset of conduct disorder (CD) with callous-unemotional traits has been linked to low levels of dopamine β-hydroxylase (DβH), an enzyme involved in dopamine turnover. The C1021T polymorphism in the DβH gene is a major quantitative-trait locus, regulating the level of DβH. In this study of juvenile delinquents from Northern Russia ( n = 180), the polymorphism at -1021 was associated neither with early-onset CD nor with psychopathic traits. Association was found between psychopathic traits and early-onset CD, ADHD and mania. [ABSTRACT FROM AUTHOR]

Abstract: The vagal motor system is involved in the regulation of cardiorespiratory and gastrointestinal functions. Vagal motor neurons are localized near or adjacent to catecholaminergic neurons, but their co-localisation seems species dependent, present in the cat but absent in the rabbit. In pig, a species commonly used as an experimental model in humans brain disorders (sudden infant death syndrome, hypoxia), the relationship is poorly understood. We aimed at describing the distribution of vagal motor neurons and tyrosine hydroxylase-immunoreactive (-ir) neurons by using a double staining method in combination with retrograde tracing of vagal efferent neurons. After fluorogold impregnation of the central part of the sectioned left cervical vagal trunk, two main vagal motor neuronal populations were located in the dorsal motor nucleus of the vagus nerve (DMX) and in the area of the nucleus ambiguus (Amb). Like in the human, the DMX was composed of different subpopulations of neurons with the same morphological characteristics. Immunohistochemistry of catecholaminergic synthesizing enzymes differentiated two main sites containing vagal motor populations: the dorsomedial and the ventrolateral medulla. TH-ir was rarely seen in vagal motor neurons of the DMX, but TH-ir neurons were present around the two main vagal motor neuronal populations that contained TH-ir fibres. The anatomical organisation of the vagal motor and the catecholaminergic neuronal systems are similar to those described in humans and suggest that the involvement of the catecholamines in the control of the vagal motor system may be similar in pigs and in humans. [Copyright &y& Elsevier]

Background: Autism spectrum disorders (ASD) are neurodevelopmental disorders of complex etiology, with a recognized substantial contribution of heterogeneous genetic factors; one of the core features of ASD is a lack of affiliative behaviors. Methods: On the basis of the existing literature, in this study we examined the hypothesis of allelic associations between genetic variants in six genes involved in control of maternal and affiliative behaviors (OXT, OXTR, PRL, PRLR, DβH, and FOSB). One hundred and seventy-seven probands with ASD from 151 families (n = 527) were assessed with a set of related instruments capturing multiple facets of ASD. Multivariate and univariate phenotypes were constructed from these assessments and subjected to genetic linkage and association analyses with PBAT and FBAT software. Results: The resulting pattern of findings, in general, confirmed the hypotheses of the significance of the genes involved in the development of affiliative behaviors in the manifestation of ASD (p values ranging from .000005 to .05); statistically speaking, the strongest results were obtained for allelic associations with the PRL, PRLR, and OXTR genes. Conclusions: These preliminary data provide additional support for the hypothesis that the allelic variants of genes necessary for the development of species-typical affiliative behaviors are associated with ASD. Independent replication of these findings is needed and studies of other genes associated with affiliative behaviors are indicated. [Copyright &y& Elsevier]

Choline acetyltransferase (ChAT) as a rate-limiting enzyme in the biosynthetic pathway of acetylcholine is thought to be present in all cholinergic neurons. However, its immunoreactivity has not been successfully applied to the study of cholinergic neurons in the pancreas. In a previous study in the pancreas of newborn guinea pig we reported the colocalization of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS) with various neuropeptides as well as dopamine-β-hydroxylase (DβH), the enzyme responsible for converting dopamine to noradrenaline. Whether NADPH-d is colocalized with ChAT in the pancreatic neurons is not known. Also it would be interesting to find out whether noradrenaline and acetylcholine could be colocalized in the same pancreatic neurons. In the present study, a method for triple labelling of ChAT, DβH and NADPH-d was used to answer the above questions. Colocalization of ChAT, DβH and NADPH-d was constantly demonstrated in the same neurons in the same sections. It is concluded that some of the pancreatic neurons may utilize more than one neurotransmitter such as nitric oxide (NO), acetylcholine and noradrenaline to achieve their function. The possible cotransmission of acetylcholine and noradrenaline was extremely intriguing, and its mechanism and significance needs to be further investigated. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation has a strong biological effect on skin biology, and it switches on adaptive mechanisms to maintain homeostasis in organs such as the skin, adrenal glands, and brain. In this study, we examined the adaptation of the body to repeated bouts of UVB radiation, especially with respect to the catecholamine synthesis pathway of the adrenal glands. The effects of UVB on catecholamine-related enzymes were determined by neurochemical and histological analyses. To evaluate catecholamine changes after chronic excessive UVB irradiation of mouse skin, we examined dopamine and norepinephrine levels in the adrenal glands and blood from UV-irradiated and sham-irradiated mice. We found that chronic excessive UVB exposure significantly reduced dopamine levels in both tissues but did not affect norepinephrine levels. In addition, UVB irradiation significantly increased the levels of related enzymes tyrosine hydroxylase and dopamine-β-hydroxylase. Furthermore, we also found that apoptosis-associated markers were increased and that oxidative defense proteins were decreased, which might have contributed to the marked structural abnormalities in the adrenal medullas of the chronically UVB-irradiated mice. This is the first evidence of the damage to the adrenal gland and subsequent dysregulation of catecholamine metabolism induced by chronic exposure to UVB. [ABSTRACT FROM AUTHOR]

Background: Sympathetic nerve wiring in the mammalian heart has remained largely unexplored. Resolving the wiring diagram of the cardiac sympathetic network would help establish the structural underpinnings of neurocardiac coupling., New Method: We used two-photon excitation fluorescence microscopy, combined with a computer-assisted 3-D tracking algorithm, to map the local sympathetic circuits in living hearts from adult transgenic mice expressing enhanced green fluorescent protein (EGFP) in peripheral adrenergic neurons., Results: Quantitative co-localization analyses confirmed that the intramyocardial EGFP distribution recapitulated the anatomy of the sympathetic arbor. In the left ventricular subepicardium of the uninjured heart, the sympathetic network was composed of multiple subarbors, exhibiting variable branching and looping topology. Axonal branches did not overlap with each other within their respective parental subarbor nor with neurites of annexed subarbors. The sympathetic network in the border zone of a 2-week-old myocardial infarction was characterized by substantive rewiring, which included spatially heterogeneous loss and gain of sympathetic fibers and formation of multiple, predominately nested, axon loops of widely variable circumference and geometry., Comparison With Existing Methods: In contrast to mechanical tissue sectioning methods that may involve deformation of tissue and uncertainty in registration across sections, our approach preserves continuity of structure, which allows tracing of neurites over distances, and thus enables derivation of the three-dimensional and topological morphology of cardiac sympathetic nerves., Conclusions: Our assay should be of general utility to unravel the mechanisms governing sympathetic axon spacing during development and disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)