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Eliane Brito Cortez Lima, Caren Nádia Soares de Sousa, Lucas Nascimento Meneses, Yuri Freitas E Silva Pereira, Natália Castelo Branco Matos, Rayanne Brito de Freitas, Nycole Brito Cortez Lima, Manoel Cláudio Azevedo Patrocínio, Luzia Kalyne Almeida Moreira Leal, Glauce Socorro Barros Viana, Silvânia Maria Mendes Vasconcelos
Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments...
October 21, 2016: Journal of Natural Medicines
Ruinan Gu, Fali Zhang, Gang Chen, Chaojun Han, Jay Liu, Zhaoxiang Ren, Yi Zhu, John L Waddington, Long Tai Zheng, Xuechu Zhen
Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). Here, we investigate the role of Clk1 in neuroinflammation and consequentially dopaminergic (DA) neuron survival. Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. Mechanistic studies demonstrated that mTOR/HIF-1α and ROS/HIF-1α signaling pathways were involved in Clk1 deficiency-induced aerobic glycolysis...
October 18, 2016: Brain, Behavior, and Immunity
Jaweed Haqparwar, Antonio Pepe, Klaus Fassbender, Ulrich Dillmann, Samer Ezziddin, Andrea Schaefer, Daniela Leppert, Jörg Spiegel
INTRODUCTION: Alpha-synuclein pathology (ASP) is a characteristic histopathological finding in idiopathic Parkinson's disease (PD). The ASP involves not only the brain but also extracranial structures. In the present study we utilized MIBG scintigraphy to measure the sympathetic innervation of the major salivary glands. We were interested in whether MIBG uptake in the major salivary glands represents a potential biomarker for ASP in PD. METHODS: We investigated 77 PD patients (age 61 ± 10 years, mean ± SD), while 15 non-PD patients (age 58 ± 15 years) with arterial hypertension, who underwent MIBG scintigraphy to exclude pheochromocytoma, served as age-matched controls...
October 15, 2016: Parkinsonism & related Disorders
A D Surowka, M Töpperwien, M Bernhardt, J D Nicolas, M Osterhoff, T Salditt, D Adamek, M Szczerbowska-Boruchowska
Human dopaminergic system in general, and substantia nigra (SN) neurons, in particular, are implicated in the pathologies underlying the human brain aging. The interplay between aberrations in the structural organization and elemental composition of SN neuron bodies has recently gained in importance as selected metals: Fe, Cu, Zn, Ca were found to trigger oxidative-stress-mediated aberration in their molecular assembly due to concomitant protein (alpha-synuclein, tau-protein) aggregation, gliosis and finally oxidative stress...
December 1, 2016: Talanta
Alessandro Minarini, Silvia Ferrari, Martina Galletti, Nina Giambalvo, Daniela Perrone, Giulia Rioli, Gian Maria Galeazzi
N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder...
October 21, 2016: Expert Opinion on Drug Metabolism & Toxicology
Amanda R de Oliveira, Adriano E Reimer, Fernando M C V Reis, Marcus L Brandão
Considering the complexity of aversive information processing and defensive response expression, a combined action of stress modulators may be required for an optimal performance during threatening situations. Dopamine is now recognized as one of the most active modulators underlying states of fear and anxiety. On the other hand, activation of hypothalamic-pituitary-adrenocortical (HPA) axis, which leads to the release of corticosterone in rodents, has been considered a key part of the stress response. The current study is an extension of prior work investigating modulatory effects of dopamine and corticosterone on conditioned fear expression...
October 20, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Chiung-Mei Chen, I-Cheng Chen, Ying-Lin Chen, Te-Hsien Lin, Wan-Ling Chen, Chih-Ying Chao, Yih-Ru Wu, Yeah-Ting Lu, Cheng-Yu Lee, Hong-Chi Chien, Ting-Shou Chen, Guey-Jen Lee-Chen, Chi-Mei Lee
BACKGROUND: The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. PURPOSE: We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP(+)-treated cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Elżbieta Lorenc-Koci, Anna Czarnecka, Kinga Kamińska, Joanna Knutelska, Małgorzata Zygmunt, Magdalena Dudek
BACKGROUND: Interaction between dopaminergic and nitrergic neurotransmission in the brain plays a crucial role in the control of motor function and in the regulation of blood pressure (BP). In Parkinson's disease (PD), dopaminergic denervation of the striatum leads to disturbances in the nitrergic system in the basal ganglia. Recently, it has been demonstrated that addition of a low dose of the nitric oxide donor molsidomine to l-DOPA therapy improves dopaminergic neurotransmission in the denervated nigrostriatal system and weakens dyskinesias in rodent models of the disease...
September 28, 2016: Pharmacological Reports: PR
Caitlin B O'Hara, Alexandra Keyes, Bethany Renwick, Katrin E Giel, Iain C Campbell, Ulrike Schmidt
In anorexia nervosa (AN), motivational salience is attributed to illness-compatible cues (e.g., underweight and active female bodies) and this is hypothesised to involve dopaminergic reward circuitry. We investigated the effects of reducing dopamine (DA) transmission on the motivational processing of AN-compatible cues in women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15). This involved the acute phenylalanine and tyrosine depletion (APTD) procedure and a startle eye-blink modulation (SEM) task...
2016: PloS One
Shelby A Montague, Bruce S Baker
An animal's ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female...
2016: PloS One
Rita Valenzuela, Maria A Costa-Besada, Javier Iglesias-Gonzalez, Emma Perez-Costas, Begoña Villar-Cheda, Pablo Garrido-Gil, Miguel Melendez-Ferro, Ramon Soto-Otero, Jose L Lanciego, Daniel Henrion, Rafael Franco, Jose L Labandeira-Garcia
The renin-angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the 'classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2)...
October 20, 2016: Cell Death & Disease
Chien-Wei Feng, Han-Chun Hung, Shi-Ying Huang, Chun-Hong Chen, Yun-Ru Chen, Chun-Yu Chen, San-Nan Yang, Hui-Min David Wang, Ping-Jyun Sung, Jyh-Horng Sheu, Kuan-Hao Tsui, Wu-Fu Chen, Zhi-Hong Wen
Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways...
October 17, 2016: Marine Drugs
Satoshi Okuyama, Tomoki Semba, Nobuki Toyoda, Francesco Epifano, Salvatore Genovese, Serena Fiorito, Vito Alessandro Taddeo, Atsushi Sawamoto, Mitsunari Nakajima, Yoshiko Furukawa
In patients with Parkinson's disease (PD), hyperactivated inflammation in the brain, particularly microglial hyperactivation in the substantia nigra (SN), is reported to be one of the triggers for the delayed loss of dopaminergic neurons and sequential motor functional impairments. We previously reported that (1) auraptene (AUR), a natural prenyloxycoumain, suppressed inflammatory responses including the hyperactivation of microglia in the ischemic brain and inflamed brain, thereby inhibiting neuronal cell death; (2) 7-isopentenyloxycoumarin (7-IP), another natural prenyloxycoumain, exerted anti-inflammatory and neuroprotective effects against excitotoxicity; and (3) 4'-geranyloxyferulic acid (GOFA), a natural prenyloxycinnamic acid, also exerted anti-inflammatory effects...
October 17, 2016: International Journal of Molecular Sciences
Qingxi Zhang, Wanling Chen, Sheng Tan, Tongxiang Lin
Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, which is characterized by low level of dopamine expressing in the striatum and deteriorated dopaminergic neurons (DAn) in Substantia nigra pars compacta (SNpc). Generation of PD-derived DAn including differentiation of human embryonic stem cell (hESC), human neural stem cell (hNSC), human induced pluripotent stem cell (hiPSC) and directly reprogramming provide an ideal tool to model PD, which created the possibilities of mimicking key essential pathological processes charactering single cell changes in vitro...
October 20, 2016: Human Gene Therapy
Thomas Viereckel, Sylvie Dumas, Casey J A Smith-Anttila, Bianca Vlcek, Zisis Bimpisidis, Malin C Lagerström, Åsa Konradsson-Geuken, Åsa Wallén-Mackenzie
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies...
October 20, 2016: Scientific Reports
Karol Cichewicz, Emma J Garren, Chika Adiele, Yoshinori Aso, Zhang Wang, Martin Wu, Serge Birman, Gerald M Rubin, Jay Hirsh
Dopamine (DA) is a neurotransmitter with conserved behavioral roles between invertebrate and vertebrate animals. In addition to its neural functions, in insects DA is a critical substrate for cuticle pigmentation and hardening. Drosophila tyrosine hydroxylase (DTH) is the rate limiting enzyme for DA biosynthesis. Viable brain DA deficient flies were previously generated using tissue selective GAL4-UAS binary expression rescue of a DTH null mutation and these flies show specific behavioral impairments. To circumvent the limitations of rescue via binary expression, here we achieve rescue utilizing genomically integrated mutant DTH...
October 19, 2016: Genes, Brain, and Behavior
Linda Chang, Gro C Løhaugen, Tamara Andres, Caroline S Jiang, Vanessa Douet, Naomi Tanizaki, Christina Walker, Deborrah Castillo, Ahnate Lim, Jon Skranes, Chad Otoshi, Eric N Miller, Thomas M Ernst
OBJECTIVES: We aimed to evaluate the effectiveness of an adaptive-working memory training (WMT) program, the corresponding neural correlates, and LMX1A-rs4657412 polymorphism on the adaptive-WMT, in HIV-participants compared to seronegative controls (SN). METHODS: 201/206 qualified participants completed baseline assessments before randomization to 25-sessions of adaptive-WMT or non-adaptive-WMT. 74/76 (34HIV, 42SN) completed adaptive-WMT and all 40 completed non-adaptive-WMT (20HIV, 20SN) and were assessed after 1-month, and 55 adaptive-WMT-participants were also assessed after 6-months...
October 19, 2016: Annals of Neurology
Aristide Merola, Alberto Romagnolo, Laura Rizzi, Mario Giorgio Rizzone, Maurizio Zibetti, Michele Lanotte, George Mandybur, Andrew P Duker, Alberto J Espay, Leonardo Lopiano
To determine the clinical and demographic correlates of persistent, remitting, and new-onset impulse control behaviors (ICBs) before and after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We compared the pre- and post-surgical prevalence of ICBs, classified as impulse control disorders (ICD), dopamine dysregulation syndrome (DDS), and punding in 150 consecutive PD STN-DBS-treated patients and determined the association with motor, cognitive, neuropsychological, and neuropsychiatric endpoints...
October 19, 2016: Journal of Neurology
Zhibin Wang, Xiao-Guang Luo, Chao Gao
In the clinic, the diagnosis of Parkinson's disease (PD) largely depends on clinicians' experience. When the diagnosis is made, approximately 80% of dopaminergic cells in the substantia nigra (SN) have been lost. Additionally, it is rather challenging to differentiate PD from atypical parkinsonian disorders (APD). Clinially-available 3T conventional MRI contributes little to solve these problems. The pathologic alterations of parkinsonism show abnormal brain iron deposition, and therefore susceptibility-weighted imaging (SWI), which is sensitive to iron concentration, has been applied to find iron-related lesions for the diagnosis and differentiation of PD in recent decades...
2016: Translational Neurodegeneration
Laurence D Picton, Keith T Sillar
Dopamine plays important roles in the development and modulation of motor control circuits. Here we show that dopamine exerts potent effects on the central pattern generator circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles. Dopamine (0.5-100 μM) reduced fictive swim bout occurrence and caused both spontaneous and evoked episodes to become shorter, slower and weaker. The D2-like receptor agonist quinpirole mimicked this repertoire of inhibitory effects on swimming, whilst the D4 receptor antagonist, L745,870, had the opposite effects...
October 20, 2016: Scientific Reports
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