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Journal of Neural Transmission

Christiane Ziegler, Katharina Domschke
Epigenetic processes such as DNA methylation are considered key mechanisms at the crossroads between genetics and environment in the etiology of mental disorders. The monoamine oxidases A and B (MAOA/MAOB) are prime candidates for the investigation into the role of DNA methylation in mental disorders, given their pivotal role in the metabolism of monoamines and as pharmacological targets of potent antidepressant drugs such as tranylcypromine, phenelzine or moclobemide. The present mini-review aims at summarizing and critically discussing the growing body of the literature supporting a role of DNA methylation of the MAOA gene promoter/exon I/intron I region and its interaction with environmental factors in several mental disorders, i...
September 21, 2018: Journal of Neural Transmission
Emily Carias, John Hamilton, Lisa S Robison, Foteini Delis, Rina Eiden, Teresa Quattrin, Michael Hadjiargyrou, David Komatsu, Panayotis K Thanos
Methylphenidate (MP) is a widely prescribed psychostimulant used to treat attention deficit hyperactivity disorder. Previously, we established a drinking paradigm to deliver MP to rats at doses that result in pharmacokinetic profiles similar to treated patients. In the present study, adolescent male rats were assigned to one of three groups: control (water), low-dose MP (LD; 4/10 mg/kg), and high dose MP (HD; 30/60 mg/kg). Following 3 months of treatment, half of the rats in each group were euthanized, and the remaining rats received only water throughout a 1-month-long abstinence phase...
September 20, 2018: Journal of Neural Transmission
Malgorzata Maciukiewicz, Ilona Gorbovskaya, Arun K Tiwari, Clement C Zai, Natalie Freeman, Herbert Y Meltzer, James L Kennedy, Daniel J Müller
Schizophrenia is a severe, debilitating disorder with a lifetime prevalence of 1% irrespective of gender or ethnicity and is typically treated with antipsychotic drugs. Antipsychotic-induced weight gain (AIWG) is a leading factor of patient non-compliance and has previously been shown to increase the risk of type 2 diabetes, metabolic syndrome, and cardiovascular events. The current study intends to replicate findings from a recent genome-wide association study in Han-Chinese patients implicating two gene variants (rs10977144 and rs10977154) of the protein tyrosine phosphatase receptor type D (PTPRD) in antipsychotic-induced weight gain (AIWG)...
September 18, 2018: Journal of Neural Transmission
Sarah Hartman, Jay Belsky
Two separate lines of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity, and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences and environmental exposures. This research considered together raises the intriguing hypothesis first advanced by Pluess and Belsky (Dev Psychopathol 23:29-38, 2011) that prenatal-stress fosters, promotes or "programs" postnatal developmental plasticity...
September 11, 2018: Journal of Neural Transmission
David Godefroy, William Rostène, Youssef Anouar, Annabelle Reaux-Le Goazigo
Working on catecholamine systems for years, the neuropharmacologist Arvid Carlsson has made a number of important and pioneering discoveries, which have highlighted the key role of these neuronal and peripheral neurotransmitters in brain functions and adrenal regulations. Since then, major advances have been made concerning the distribution of the catecholaminergic systems in particular by studying their rate-limiting enzyme, tyrosine hydroxylase (TH). Recently new methods of tissue transparency coupled with in toto immununostaining and three-dimensional (3D) imaging technologies allow to precisely map TH immunoreactive pathways in the mouse brain and adrenal glands...
September 11, 2018: Journal of Neural Transmission
Cosima Rhein, Stefan Löber, Peter Gmeiner, Erich Gulbins, Philipp Tripal, Johannes Kornhuber
In recent studies, major depressive disorder (MDD) was linked to an increase in acid sphingomyelinase (ASM) activity. Several drugs that are commonly used to treat MDD functionally inhibit the lysosomal enzyme ASM and are called functional inhibitors of ASM (FIASMAs). These drugs are classified as cationic amphiphilic drugs (CADs) that influence the catalytic activities of different lysosomal enzymes. This action results in the side effect of phospholipidosis (PLD), which describes a detrimental increase in the phospholipid content in lysosomes...
September 6, 2018: Journal of Neural Transmission
Sam Mostafa, Carl M J Kirkpatrick, Keith Byron, Leslie Sheffield
Common polymorphisms in the genes encoding CYP2D6, CYP2C19, CYP2C9 and VKORC1 enzymes have an important role in predicting the occurrence of adverse effects and the efficacy of substrate medications. Drug-induced changes to the enzyme's phenotype, a process called phenoconversion, comprise another important factor contributing to interindividual variability in drug response. To date, there is lack of data on the frequency of these common polymorphisms and phenoconversion in the pan-ethnic Australian population...
September 6, 2018: Journal of Neural Transmission
Ivan Milenkovic, Alexander Zimprich, Martin Gencik, Kirsten Platho-Elwischger, Stefan Seidel
We present a family with two members affected by hyperekplexia and two unaffected members. All exons in the glycine receptor alpha 1 subunit gene (GLRA1) were sequenced in all four family members. Our index patient harbored a novel nonsense mutation (p.Trp314*; rs867618642) in the transmembrane domain three of the GLRA1 and a novel missense variant in the NH2 -terminal part (p.Val67Met; rs142888296). After development of tolerance for the effective treatment with clobazam a drug holiday led to a sustained restoration of the treatment response...
September 4, 2018: Journal of Neural Transmission
Luca Giacinto Iacovino, Francesca Magnani, Claudia Binda
The first crystal structure of mammalian monoamine oxidases (MAOs) was solved in 2002; almost 65 years after, these FAD-dependent enzymes were discovered and classified as responsible for the oxidation of aromatic neurotransmitters. Both MAO A and MAO B feature a two-domain topology characterized by the Rossmann fold, interacting with dinucleotide cofactors, which is intimately associated to a substrate-binding domain. This globular body is endowed with a C-terminal α-helix that anchors the protein to the outer mitochondrial phospholipid bilayer...
August 24, 2018: Journal of Neural Transmission
Jeanne Mialet-Perez, Yohan Santin, Angelo Parini
The mitochondrial enzyme monoamine oxidase A (MAO-A) is widely distributed in neuronal, myocyte and non-myocyte cardiac compartments. After the demonstrations that both cardiac neuronal and extraneuronal MAO-A contribute to the degradation of norepinephrine and serotonin, several studies attempted to determine the impact of MAO-A activity in the control of local concentration of the two biogenic amines and in their receptor-mediated effects. From the 2000s, an additional mechanism of action of MAO-A has been proposed...
July 24, 2018: Journal of Neural Transmission
Angelo Antonini, Bianca Nitu
Development of motor fluctuations and dyskinesia characterizes the transition from early to advanced Parkinson disease stage. Current therapeutic strategies to manage motor complications aim at increasing the number of levodopa administrations and extending its benefit by the association of enzyme blockers and dopamine agonists. However, as disease progresses, mobility becomes progressively dependent on levodopa absorption and its plasma bioavailability, resulting in loss of independence, worse quality of life and increased caregiver burden...
July 13, 2018: Journal of Neural Transmission
Young-Kyoung Ryu, Hye-Yeon Park, Jun Go, Yong-Hoon Kim, Jung Hwan Hwang, Dong-Hee Choi, Jung-Ran Noh, Myungchull Rhee, Pyung-Lim Han, Chul-Ho Lee, Kyoung-Shim Kim
Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on L-DOPA-induced dyskinesia of Parkinson's disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of L-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model...
July 11, 2018: Journal of Neural Transmission
Toshiharu Nagatsu, Akira Nakashima, Hiroshi Ichinose, Kazuto Kobayashi
Parkinson's disease (PD) is an aging-related movement disorder mainly caused by a deficiency of neurotransmitter dopamine (DA) in the striatum of the brain and is considered to be due to progressive degeneration of nigro-striatal DA neurons. Most PD is sporadic without family history (sPD), and there are only a few percent of cases of young-onset familial PD (fPD, PARKs) with the chromosomal locations and the genes identified. Tyrosine hydroxylase (TH), tetrahydrobiopterin (BH4)-dependent and iron-containing monooxygenase, catalyzes the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which is the initial and rate-limiting step in the biosynthesis of catecholamines (DA, noradrenaline, and adrenaline)...
July 11, 2018: Journal of Neural Transmission
Udo Bonnet, Dieter Bingmann, Erwin-Josef Speckmann, Martin Wiemann
The intracellular pH (pHi) in the cytosol of mammalian central neurons is tightly regulated and small pHi-fluctuations are deemed to modulate inter-/intracellular signaling, excitability, and synaptic plasticity. The resting pHi of young rodent hippocampal pyramidal neurons is known to decrease alongside aging for about 0.1 pH-units. There is no information about the relationship between age and pHi of human central neurons. We addressed this knowledge gap using 26 neocortical slices from 12 patients (1-56-years-old) who had undergone epilepsy surgery...
July 11, 2018: Journal of Neural Transmission
Yoshihiro Miyake, Keiko Tanaka, Masashi Arakawa
ITIH3 and ITIH4 are involved in the stabilization of the extracellular matrix. Several genome-wide association studies and case-control studies regarding psychiatric disorders have identified ITIH3 and ITIH4 single nucleotide polymorphisms (SNPs). The present case-control study examined the relationship between ITIH3 SNPs rs2535629 and rs736408 and ITIH4 SNPs rs3821831 and rs2239547 and depressive symptoms during pregnancy in Japan. Cases comprised 273 women with depressive symptoms during pregnancy defined as a Center for Epidemiological Studies Depression Scale (CES-D) score ≥ 16...
July 10, 2018: Journal of Neural Transmission
Odette Fründt, Tina Mainka, Beate Schönwald, Bianca Müller, Polina Dicusar, Christian Gerloff, Carsten Buhmann
To close a gap between inpatient and outpatient care, the Hamburg Parkinson day-clinic (HPDC) has been developed as a new and comprehensive, individual, interdisciplinary type of treatment for patients with complex Parkinsonian syndromes (PS). First, we describe the HPDC concept, in which a multi-professional medical team of PD specialists provide a time- and personnel-wise intensive care and focuses on the patients' individual deficits and resources. Second, we present short-term outcome results of the first 184 PS patients enrolled during 16 months including objective clinical motor and non-motor scores taken before and after participation in the HPDC, as well as the patients' subjective evaluation of the HPDC...
October 2018: Journal of Neural Transmission
Dilara Yüksel, Jennifer Engelen, Verena Schuster, Bruno Dietsche, Carsten Konrad, Andreas Jansen, Udo Dannlowski, Tilo Kircher, Axel Krug
Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years...
October 2018: Journal of Neural Transmission
Hidetomo Murakami, Ken Yamamoto, Taro Yasumoto, Atsushi Kimura, Yoshiki Sakae, Shohei Nomoto, Satomi Kubota, Daishi Watanabe, Keiko Watanabe, Yu Saito, Satoshi Yano, Kenjiro Ono
We examined the correlations between cerebrospinal fluid (CSF) concentrations of homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) and imaging assessment scores, using 123 I-Ioflupane SPECT and 123 I-MIBG myocardial scintigraphy in 23 drug naïve PD patients. The CSF 5-HIAA concentration correlated with the H/M ratio of the delayed image (r = 0.458, p < 0.05) and the washout rate (r = - 0.642, p < 0.01) of 123 I-MIBG myocardial scintigraphy. These correlations suggest some unclarified pathophysiological links between the central serotonergic and cardiac sympathetic systems...
October 2018: Journal of Neural Transmission
Mirko Bibl, Marion Gallus, Volker Welge, Hermann Esselmann, Stefanie Wolf, Eckart Rüther, Jens Wiltfang
The respective first and last authors of this article, Mirko Bibl and Jens Wiltfang, would like to clarify the issue of the seeming duplicate publication of a figure in two articles.
October 2018: Journal of Neural Transmission
Ilaria Cova, Alberto Priori
Parkinson's disease (PD) is a neurodegenerative disorder whose aetiology remains unclear: degeneration involves several neurotransmission systems, resulting in a heterogeneous disease characterized by motor and non-motor symptoms. PD causes progressive disability that responds only to symptomatic therapies. Future advances include neuroprotective strategies for use in at-risk populations before the clinical onset of disease, hence the continuing need to identify reliable biomarkers that can facilitate the clinical diagnosis of PD...
October 2018: Journal of Neural Transmission
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