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https://www.readbyqxmd.com/read/28088287/insulin-like-growth-factor-binding-protein-3-deficiency-leads-to-behavior-impairment-with-monoaminergic-and-synaptic-dysfunction
#1
Hongmei Dai, Yu-Ichi Goto, Masayuki Itoh
Insulin-like growth factor binding protein (IGFBP)-3 regulates IGF bioactivity, induces apoptosis, and inhibits cell growth independent of IGFs, but the functional role of IGFBP3 in the brain is not clear. In the present study, we revealed the effect of IGFBP3 on the brain by characterizing the phenotype of Igfbp3-null mice. Compared with wild-type mice, Igfbp3-null mice had significantly decreased IGF-1 content in the brain but no change in weights of brain and body. In Igfbp3-null mice, the number of dendritic spines was significantly reduced, and the dendritic diameter was thickening...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28087060/personality-in-parkinson-s-disease-clinical-behavioural-and-cognitive-correlates
#2
REVIEW
Gabriella Santangelo, Fausta Piscopo, Paolo Barone, Carmine Vitale
Affective disorders and personality changes have long been considered pre-motor aspects of Parkinson's disease (PD). Many authors have used the term "premorbid personality" to define distinctive features of PD patients' personality characterized by reduced exploration of new environmental stimuli or potential reward sources ("novelty seeking") and avoidance behaviour ("harm avoidance") present before motor features. The functional correlates underlying the personality changes described in PD, implicate dysfunction of meso-cortico-limbic and striatal circuits...
January 5, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28075498/tamoxifen-and-its-active-metabolites-inhibit-dopamine-transporter-function-independently-of-the-estrogen-receptors
#3
Sarah R Mikelman, Bipasha Guptaroy, Margaret Gnegy
As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [(3) H]dopamine uptake into hDAT-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake...
January 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072417/dopaminergic-dynamics-underlying-sex-specific-cocaine-reward
#4
Erin S Calipari, Barbara Juarez, Carole Morel, Deena M Walker, Michael E Cahill, Efrain Ribeiro, Ciorana Roman-Ortiz, Charu Ramakrishnan, Karl Deisseroth, Ming-Hu Han, Eric J Nestler
Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28062370/treadmill-exercise-alleviates-motor-deficits-and-improves-mitochondrial-import-machinery-in-an-mptp-induced-mouse-model-of-parkinson-s-disease
#5
Jung-Hoon Koo, Joon-Yong Cho, Ung-Bae Lee
Alpha-synuclein (α-Syn) accumulation is significantly correlated with motor deficits and mitochondrial dysfunction in Parkinson's disease (PD), but the molecular mechanism underlying its pathogenesis is unclear. In this study, we investigated the effects of treadmill exercise on motor deficits and mitochondrial dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treadmill exercise inhibited dopaminergic neuron loss by promoting the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and seemed to improve cell survival by reducing α-Syn expression...
January 3, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28062203/semi-mechanistic-computer-simulation-of-psychotic-symptoms-in-schizophrenia-with-a-model-of-a-humanized-cortico-striatal-thalamocortical-loop
#6
Athan Spiros, Patrick Roberts, Hugo Geerts
Despite new insights into the pathophysiology of schizophrenia and clinical trials with highly selective drugs, no new therapeutic breakthroughs have been identified. We present a semi-mechanistic Quantitative Systems Pharmacology (QSP) computer model of a biophysically realistic cortical-striatal-thalamo-cortical loop. The model incorporates the direct, indirect and hyperdirect pathway of the basal ganglia and CNS drug targets that modulate neuronal firing, based on preclinical data about their localization and coupling to voltage-gated ion channels...
January 3, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28060209/catechol-o-methyltransferase-genotypes-and-parenting-influence-on-long-term-executive-functioning-after-moderate-to-severe-early-childhood-traumatic-brain-injury-an-exploratory-study
#7
Brad G Kurowski, Amery Treble-Barna, Huaiyu Zang, Nanhua Zhang, Lisa J Martin, Keith Owen Yeates, H Gerry Taylor, Shari L Wade
OBJECTIVES: To examine catechol-O-methyltransferase (COMT) rs4680 genotypes as moderators of the effects of parenting style on postinjury changes in parent behavior ratings of executive dysfunction following moderate to severe early childhood traumatic brain injury. SETTING: Research was conducted in an outpatient setting. PARTICIPANTS: Participants included children admitted to hospital with moderate to severe traumatic brain injury (n = 55) or orthopedic injuries (n = 70) between ages 3 and 7 years...
January 5, 2017: Journal of Head Trauma Rehabilitation
https://www.readbyqxmd.com/read/28053029/mutant-%C3%AE-synuclein-overexpression-induces-stressless-pacemaking-in-vagal-motoneurons-at-risk-in-parkinson-s-disease
#8
Efrat Lasser-Katz, Alon Simchovitz, Wei-Hua Chiu, Wolfgang H Oertel, Ronit Sharon, Hermona Soreq, Jochen Roeper, Joshua A Goldberg
: α-Synuclein overexpression (ASOX) drives the formation of toxic aggregates in neurons vulnerable in Parkinson's disease (PD), including dopaminergic neurons of the substantia nigra (SN) and cholinergic neurons of the dorsal motor nucleus of the vagus (DMV). Just as these populations differ in when they exhibit α-synucleinopathies during PD pathogenesis, they could also differ in their physiological responses to ASOX. An ASOX-mediated hyperactivity of SN dopamine neurons, which was caused by oxidative dysfunction of Kv4...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28052095/metabolomic-profiling-in-individuals-with-a-failing-kidney-allograft
#9
Roberto Bassi, Monika A Niewczas, Luigi Biancone, Stefania Bussolino, Sai Merugumala, Sara Tezza, Francesca D'Addio, Moufida Ben Nasr, Alessandro Valderrama-Vasquez, Vera Usuelli, Valentina De Zan, Basset El Essawy, Massimo Venturini, Antonio Secchi, Francesco De Cobelli, Alexander Lin, Anil Chandraker, Paolo Fiorina
BACKGROUND: Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. METHODS: To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3)...
2017: PloS One
https://www.readbyqxmd.com/read/28050184/lack-of-association-between-dopamine-beta-hydroxylase-dbh-19-bp-insertion-deletion-polymorphism-and-risk-of-schizophrenia
#10
Mansour Shakiba, Mohammad Hashemi, Sara Shahrabadi, Maryam Rezaei, Mohsen Taheri
Objective: Interaction between genetic and environmental factors is considered as major factors in Schizophrenia (SCZ). It has been shown that dopaminergic and noradrenergic neurotransmission dysfunction play an essential role in the SCZ pathogenesis. This study aimed to find the impact of functional 19-bp insertion/deletion (ins/del) polymorphism in dopamine beta-hydroxylase (DBH) gene on SCZ risk in a sample of Iranian population. Method: This case-control study was conducted on 109 SCZ patients and 116 matched healthy subjects...
October 2016: Iranian Journal of Psychiatry
https://www.readbyqxmd.com/read/28041956/basal-ganglia-dysfunction-contributes-to-physical-inactivity-in-obesity
#11
Danielle M Friend, Kavya Devarakonda, Timothy J O'Neal, Miguel Skirzewski, Ioannis Papazoglou, Alanna R Kaplan, Jeih-San Liow, Juen Guo, Sushil G Rane, Marcelo Rubinstein, Veronica A Alvarez, Kevin D Hall, Alexxai V Kravitz
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice...
December 20, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28027110/unaltered-dopamine-transporter-availability-in-drug-naive-patients-with-schizophrenia-after-6-months-of-antipsychotics-treatment-a-naturalistic-study
#12
Wei Hung Chang, Kao Chin Chen, I Hui Lee, Mei Hung Chi, Po See Chen, Wei Jen Yao, Nan Tsing Chiu, Yen Kuang Yang
BACKGROUND: Dopaminergic dysfunction, namely, dopamine transporter (DAT) availability variations in patients with drug-naive schizophrenia after long-term treatment, is still not well understood. The aims of the study were to explore (i) whether the DAT availability in patients with drug-naive schizophrenia differed after antipsychotic treatment and (ii) whether treatment with different generations of antipsychotics influenced the DAT availability after follow-up for 6 months. METHODS: Twenty-four first-episode, drug-naive patients with schizophrenia were divided into first- and second-generation antipsychotic groups naturalistically...
February 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28025939/serotonin-selective-reuptake-inhibitors-ssris-and-female-sexual-dysfunction-fsd-hypothesis-on-its-association-and-options-of-treatment
#13
Nurul Azmi Mahamad Rappek, Hatta Sidi, Jaya Kumar, Sazlina Kamarazaman, Srijit Das, Ruziana Masiran, Najwa Baharudin, Muhammad Hatta
Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter-playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potentially confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies...
December 27, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28025067/dopamine-d1-like-receptor-in-lateral-habenula-nucleus-affects-contextual-fear-memory-and-long-term-potentiation-in-hippocampal-ca1-in-rats
#14
Jiangping Chan, Xin Guan, Yiling Ni, Lilu Luo, Liqiang Yang, Pengyue Zhang, Jichuan Zhang, Yanmei Chen
The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats...
December 23, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/28017790/the-cb1-receptor-is-required-for-the-establishment-of-the-hyperlocomotor-phenotype-in-developmentally-induced-hypothyroidism-in-mice
#15
Elena Giné, Victor Echeverry-Alzate, Jose Antonio Lopez-Moreno, Fernando Rodriguez de Fonseca, Ana Perez-Castillo, Angel Santos
Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R(-/-)) and in their wild type littermates (CB1R(+/+)), whose hypothyroidism was induced in day 12 of gestation and maintained during the experimental period...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28008793/social-isolation-alters-central-nervous-system-monoamine-content-in-prairie-voles-following-acute-restraint
#16
Neal McNeal, Eden M Anderson, Deirdre Moenk, Diane Trahanas, Leslie Matuszewich, Angela J Grippo
Animal models have shown that social isolation and other forms of social stress lead to depressive- and anxiety-relevant behaviors, as well as neuroendocrine and physiological dysfunction. The goal of this study was to investigate the effects of prior social isolation on neurotransmitter content following acute restraint in prairie voles. Animals were either paired with a same-sex sibling or isolated for four weeks. Plasma adrenal hormones and ex vivo tissue concentrations of monoamine neurotransmitters and their metabolites were measured following an acute restraint stressor in all animals...
December 23, 2016: Social Neuroscience
https://www.readbyqxmd.com/read/28003467/prefrontal-cortex-dysfunction-increases-susceptibility-to-schizophrenia-like-changes-induced-by-adolescent-stress-exposure
#17
Felipe V Gomes, Anthony A Grace
Stress during adolescence is a risk factor for schizophrenia, and medial prefrontal cortex (mPFC) dysfunction is proposed to interfere with stress control, increasing the susceptibility to stress. We evaluated the impact of different stressful events during adolescence (restraint stress [RS], footshock [FS], or the combination of FS and RS) on behaviors correlated with schizophrenia in rats as adults. At adulthood, animals were tested for anxiety responses (elevated plus-maze), cognitive function (novel-object recognition test) and dopamine (DA) system responsivity (locomotor response to amphetamine and DA neuron activity in the ventral tegmental area (VTA) using in vivo electrophysiology)...
December 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27996211/gsk-3%C3%AE-interacts-with-dopamine-d1-receptor-to-regulate-receptor-function-implication-for-prefrontal-cortical-d1-receptor-dysfunction-in-schizophrenia
#18
Jing-Ru Wang, Pei-Hua Sun, Zhao-Xiang Ren, Herbert Y Meltzer, Xue-Chu Zhen
INTRODUCTION: Impaired dopamine D1 receptor (D1R) function in prefrontal cortex (PFC) is believed to contribute to the PFC hypofunction that has been hypothesized to be associated with negative symptoms and cognitive deficits in schizophrenia. It is therefore critical to understand the mechanisms for modulation of D1R function. AIMS: To investigate the physical interaction and functional modulation between D1R and GSK-3β. RESULTS: D1R and GSK-3β physically interact in cultured cells and native brain tissues...
December 20, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27995639/glucose-rich-diet-aggravates-monocrotophos-induced-dopaminergic-neuronal-dysfunction-in-caenorhabditis-elegans
#19
Chinnu Salim, P S Rajini
The present study aimed to obtain insights into the mechanism(s) by which glucose-rich diet aggravates monocrotophos (MCP)-induced dopaminergic neuronal dysfunction in Caenorhabditis elegans. In this study, we exposed three different strains of worms (wild-type N2, CB1112 (cat-2(e1112)II, tyrosine hydroxylase-deficient mutant, catecholamine absent) and the transgenic BZ555 (egls1-dat-1p::green fluorescent protein [GFP]) (in which bright GFP is tagged to the dopamine neuronal soma and processes) grown and maintained in normal nematode growth medium or 2% glucose enriched-nematode growth medium to MCP (0...
December 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27989675/optogenetic-stimulation-of-frontal-d1-neurons-compensates-for-impaired-temporal-control-of-action-in-dopamine-depleted-mice
#20
Young-Cho Kim, Sang-Woo Han, Stephanie L Alberico, Rafael N Ruggiero, Benjamin De Corte, Kuan-Hua Chen, Nandakumar S Narayanan
Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson's disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1-4 Hz) in the medial frontal cortex (MFC) during interval timing...
January 9, 2017: Current Biology: CB
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