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Alessandro Tessitore, Pietro Marano, Nicola Modugno, Francesco E Pontieri, Nicola Tambasco, Margherita Canesi, Anna Latorre, Leonardo Lopiano, Mariachiara Sensi, Rocco Quatrale, Paolo Solla, Giovanni Defazio, Gabriella Melzi, Anna Maria Costanzo, Giuliana Gualberti, Umberto di Luzio Paparatti, Angelo Antonini
INTRODUCTION: Caring for a person with Parkinson's disease (PD) is associated with an increased risk of psychiatric morbidity and persistent distress. The objective of this study was to describe the burden and the related factors of caregivers of advanced PD (APD) patients either treated with continuous dopaminergic delivery systems or standard therapy. METHODS: This cross-sectional, epidemiologic study conducted in 13 Italian sites enrolled PD patients treated with continuous dopaminergic delivering systems [either levodopa/carbidopa intestinal gel (LCIG) infusion or continuous subcutaneous apomorphine infusion (CSAI)] or continuation of standard of care (SOC) with a caregiver...
March 7, 2018: Journal of Neurology
Teresa Mann, Jens Kurth, Alexander Hawlitschka, Jan Stenzel, Tobias Lindner, Stefan Polei, Alexander Hohn, Bernd J Krause, Andreas Wree
Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D₂/D₃ receptor (D₂/D₃R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [18 F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection...
March 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yanyan Wang, Yong Wang, Junhua Liu, Xiaomin Wang
Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks...
March 5, 2018: Neuroscience Bulletin
Yuan-Hao Chen, Tung-Tai Kuo, Jen-Hsin Kao, Eagle Yi-Kung Huang, Tsung-Hsun Hsieh, Yu-Ching Chou, Barry J Hoffer
To determine the influences of exercise on motor deficits and dopaminergic transmission in a hemiparkinson animal model, we measured the effects of exercise on the ambulatory system by estimating spatio-temporal parameters during walking, striatal dopamine (DA) release and reuptake and synaptic plasticity in the corticostriatal pathway after unilateral 6-OHDA lesions. 6-OHDA lesioned hemiparkinsonian rats were exercised on a fixed speed treadmill for 30 minutes per day. Controls received the same lesion but no exercise...
March 5, 2018: Scientific Reports
Nicola Simola, Giulia Costa
The emission of 50-kHz ultrasonic vocalizations (USVs) is increasingly emerging as a potential behavioral marker of the subjective effects that psychoactive drugs elicit in rats. However, multiple categories of 50-kHz USVs have been identified, which are thought to possess different behavioral significance. Besides, limited information is available on how psychoactive drugs affect the emission of categorized 50-kHz USVs. To further elucidate this issue, we evaluated the numbers of multiple categories of 50-kHz USVs emitted by rats repeatedly treated with amphetamine (1 or 2 mg/kg, i...
March 2, 2018: Behavioural Brain Research
Merlin Lange, Cynthia Froc, Hannah Grunwald, William H J Norton, Laure Bally-Cuif
Polymorphisms in the gene coding for the adhesion G-protein coupled receptor LPHN3 are a risk factor for attention-deficit/hyperactivity disorder (ADHD). Transient down-regulation of latrophilin3.1 (lphn3.1), the zebrafish LPHN3 homologue, causes hyperactivity. Zebrafish injected with a lphn3.1-specific morpholino are hyperactive and display an impairment in dopaminergic neuron development. In the present study we used lphn3.1 morphants to further characterize the changes to dopaminergic signaling that trigger hyperactivity...
February 26, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Anette Bro Christensen, Jens Christian Hedemann Sørensen, Kåre Schmidt Ettrup, Dariusz Orlowski, Carsten Reidies Bjarkam
INTRODUCTION: The rotating 6-hydroxydopamine (6-OHDA) rat model has long been important when developing new treatment strategies for Parkinson's disease (PD). Similar non-human primate models have been developed for translational research purposes as large animal models are required by regulatory bodies as an intermediate "phase 0" trial step. However, experimental research in non-human primates encounters several economical and regulatory issues, which may be avoided by the alternative use of pigs as a large animal model for experimental brain research...
February 17, 2018: Brain Research Bulletin
Mizuho Hanaki, Kazuma Murakami, Sumie Katayama, Ken-Ichi Akagi, Kazuhiro Irie
(R)-Apomorphine (1) has the potential to reduce the accumulation of amyloid β-protein (Aβ42), a causative agent of Alzheimer's disease (AD). Although the inhibition of Aβ42 aggregation by 1 is ascribable to the antioxidative effect of its phenol moiety, its inhibitory mechanism at the molecular level remains to be fully elucidated. LC-MS and UV analyses revealed that 1 is autoxidized during incubation to produce an unstable o-quinone form (2), which formed a Michael adduct with Lys 16 and 28 of Aβ42. A further autoxidized form of 1 (3) with o-quinone and phenanthrene moieties suppressed Aβ42 aggregation comparable to 1, whereas treating 1 with a reductant, tris(2-carboxyethyl)phosphine diminished its inhibitory activity...
February 2, 2018: Bioorganic & Medicinal Chemistry
T Mann, K Zilles, H Dikow, A Hellfritsch, M Cremer, M Piel, F Rösch, A Hawlitschka, O Schmitt, A Wree
Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D1, D2/D3, α 1, α 2, and 5HT2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography...
February 5, 2018: Neuroscience
Antti Huotarinen, Anna-Maija Penttinen, Susanne Bäck, Merja H Voutilainen, Ulrika Julku, T Petteri Piepponen, Pekka T Männistö, Mart Saarma, Raimo Tuominen, Aki Laakso, Mikko Airavaara
Several neurotrophic factors (NTF) are shown to be neuroprotective and neurorestorative in pre-clinical animal models for Parkinson's disease (PD), particularly in models where striatal dopamine neuron innervation partially exists. The results of clinical trials on late-stage patients have been modest. Subthalamic deep brain stimulation (STN DBS) is a proven treatment for a selected group of advanced PD patients. The cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic protein, but its effects in animal models of late-stage PD have remained under-researched...
March 15, 2018: Neuroscience
Hideaki Yano, Ning-Sheng Cai, Min Xu, Ravi Kumar Verma, William Rea, Alexander F Hoffman, Lei Shi, Jonathan A Javitch, Antonello Bonci, Sergi Ferré
The two highly homologous subtypes of stimulatory G proteins Gαs (Gs) and Gαolf (Golf) display contrasting expression patterns in the brain. Golf is predominant in the striatum, while Gs is predominant in the cortex. Yet, little is known about their functional distinctions. The dopamine D1 receptor (D1R) couples to Gs/olf and is highly expressed in cortical and striatal areas, making it an important therapeutic target for neuropsychiatric disorders. Using novel drug screening methods that allow analysis of specific G-protein subtype coupling, we found that, relative to dopamine, dihydrexidine and N-propyl-apomorphine behave as full D1R agonists when coupled to Gs, but as partial D1R agonists when coupled to Golf...
February 5, 2018: Nature Communications
Xueliang Fan, Yuping Donsante, H A Jinnah, Ellen J Hess
Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general view that dopaminergic drugs are ineffective. However, there is little conclusive evidence to support or refute this assumption. Therefore, to assess the therapeutic potential of these compounds, we analyzed results from multiple trials of dopamine receptor agonists in patients with idiopathic dystonias and also tested the efficacy of dopamine receptor agonists in a mouse model of generalized dystonia...
January 18, 2018: Journal of Pharmacology and Experimental Therapeutics
Bao-Dong Li, Jing-Jun Cui, Jia Song, Ce Qi, Pei-Feng Ma, Ya-Rong Wang, Jing Bai
BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD...
January 15, 2018: Cellular Physiology and Biochemistry
Manon Auffret, Sophie Drapier, Marc Vérin
The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson's disease (PD). The chemistry, structure-activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic...
January 11, 2018: Clinical Drug Investigation
Joan Duprez, Jean-François Houvenaghel, Sophie Drapier, Manon Auffret, Dominique Drapier, Gabriel Robert, Marc Vérin, Paul Sauleau
INTRODUCTION: Continuous subcutaneous apomorphine infusion (CSAI) is increasingly used in Parkinson's disease (PD), notably in patients contraindicated for subthalamic deep brain stimulation. Although it has been suggested that CSAI is safe regarding cognition, few studies have actually investigated its effect, especially on cognitive control which is a crucial process for goal-directed behavior. More specifically, its impact on the dynamics of cognitive action control, as reflected by the activation and suppression of impulsive responses, has yet to be investigated, which is the objective of the present study...
March 2018: Journal of Neurology
Guotao Chen, Baibing Yang, Jianhuai Chen, Leilei Zhu, Hesong Jiang, Wen Yu, Fengchao Zang, Yun Chen, Yutian Dai
BACKGROUND: Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. AIM: To develop a noED animal model based on chronic mild stress and investigate brain activity changes. METHODS: We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state...
December 20, 2017: Journal of Sexual Medicine
Salvatore Galati, Song Wei, Gergely Orban, Andreas R Luft, Alain Kaelin-Lang
Urethane-induced cortical slow wave activity (SWA) spreads into the basal ganglia in dopamine (DA)-depleted rat models of Parkinson's disease (PD). During physiological sleep, SWA is powerfully expressed at the beginning of night and progressively reduced during sleep-time reflecting the sleep need. However, its underlying slow oscillations may contribute directly to modulate cortical plasticity. In order to determine the impact of the SWA on synaptic strength and its interplay with DA, we simultaneously recorded the electrocorticogram (ECoG) and the corticocortical- and corticostriatal-evoked potentials (CC-EPs, CS-EPs) during eight hours of robust urethane-induced SWA in both normal and PD animals...
December 15, 2017: Experimental Neurology
Mohammad Reza Sarookhani, Hashem Haghdoost-Yazdi, Ali Sarbazi-Golezari, Arvin Babayan-Tazehkand, Nafiseh Rastgoo
Studies have shown that hydrogen sulfide (H2S) exerts a neuroprotective effect and may have a therapeutic value for treating neurodegenerative diseases including Parkinson's disease. However, little is known about the mechanisms underlying the neuroprotective activity of H2S in vivo. Here, we evaluated the effect of glibenclamide, an ATP-sensitive potassium channel blocker, on the neuroprotective activity of H2S in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson's disease. 6-OHDA was administered by stereotaxic surgery into the medial forebrain bundle...
December 12, 2017: Behavioural Pharmacology
Patrick Amoateng, Dorcas Osei-Safo, Kennedy Kwami Edem Kukuia, Samuel Adjei, Obed Awintuma Akure, Constance Agbemelo-Tsomafo, Shirley Nyarko Adu-Poku, Kenneth Yaw Agyeman-Badu
Background: Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia (AZE) may possess antipsychotic and antidepressant properties. Method: The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system. The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
F Mastroiacovo, A Gaglione, C L Busceti, L Ryskalin, G Bozza, F Nicoletti, F Orzi, F Fornai
The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat...
September 1, 2017: Archives Italiennes de Biologie
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