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Hussain N Alhamami, Md Main Uddin, A S M Hasan Mahmood, Karen P Briski
The hypothalamic energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK), an important regulator of counter-regulatory responses to hypoglycemia, responds to pharmacological manipulation of hindbrain AMPK activity. Dorsomedial hindbrain A2 noradrenergic neurons express hypoglycemia-sensitive metabolo-sensory biomarkers, including AMPK. Here, adult male rats were pretreated by intra-caudal fourth ventricular administration of the selective neurotoxin 6-hydroxydopamine (6-OHDA) to determine if catecholamine signaling from the aforesaid site governs hypothalamic AMPK activation during insulin-induced hypoglycemia (IIH)...
March 10, 2018: Neuroscience
P A Caro Aponte, C A Otálora, J C Guzmán, L F Turner, J P Alcázar, E L Mayorga
Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i)develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii)evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM)...
March 7, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Liying Yang, Hongyan Wang, Lijun Liu, Anmu Xie
Dementia, a condition that frequently afflicts patients in advanced stages of Parkinson's disease (PD), results in decreased quality of life and survival time. Nevertheless, the pathological mechanisms underlying Parkinson's disease dementia (PDD) are not completely understood. The symptoms characteristic of PDD may be the result of functional and structural deficiencies. The present study implicates the accumulation of Lewy bodies in the cortex and limbic system as a potent trigger in the development of PDD...
2018: Frontiers in Neuroscience
Yingjuan Liu, Lihua Geng, Jingjing Zhang, Jing Wang, Qi Zhang, Delin Duan, Quanbin Zhang
Parkinson's disease (PD) is a neurodegenerative movement disorder that is caused by a selective loss of dopaminergic neurons. Current PD treatments provide symptomatic relief but do not prevent or decelerate disease progression. Previous studies have suggested that acetylated and phosphorylated porphyran, derived from Porphyra , produces a neuroprotective effect against 6-OHDA-induced damage. Due to its antioxidant and neuroprotective potential, this study evaluates whether oligo-porphyran (OP) could be beneficial in an experimental model of PD in mice...
March 6, 2018: Marine Drugs
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
Hossein Haddadi, Ziba Rajaei, Hojjatallah Alaei, Somayeh Shahidani
The present study investigated the effects of carvacrol on motor and memory deficits as well as hyperalgesia in the 6-OHDA-lesioned rat model of Parkinson's disease. The animals were subjected to unilateral microinjection of 6-OHDA into the medial forebrain bundle and treated with carvacrol (25, 50 and 100 mg/kg, ip) for six weeks after surgery. The 6-OHDA-lesioned rats showed contralateral rotations towards the lesion side, which was accompanied by learning and memory deficits in a passive avoidance test and a decrease in tail withdrawal latency in a tail flick test at the end of week 6...
February 2018: Arquivos de Neuro-psiquiatria
Luz M Suarez, Samuel Alberquilla, Jose R García-Montes, Rosario Moratalla
In toxin-based models of Parkinson's disease (PD), striatal projection neurons (SPNs) exhibit dendritic atrophy and spine loss concurrent with an increase in excitability. Chronic L-DOPA-treatment that induces dyskinesia selectively restores spine density and excitability in indirect pathway SPNs (iSPNs), whereas spine loss and hyper-excitability persist in direct pathway SPNs (dSPNs). These alterations have only been characterized in toxin-based models of PD, raising the possibility that they are an artifact of exposure to the toxin, which may engage compensatory mechanisms independent of the PD-like pathology or due to the loss of dopaminergic afferents...
February 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
P S de Campos, L R S M Kawamura, K Hasegawa, Y Kumei, J L Zeredo
Parkinson's disease (PD) is known to cause tremor and rigidity, but other symptoms such as respiratory and autonomic dysfunctions are a major cause of disability and mortality in patients. In this study, we examined respiratory movements by using cineradiography on a murine model of late/advanced PD. Under surgical anesthesia, C57BL/6J mice received an injection of either 6-OHDA or vehicle solution to the right striatum. Two weeks after surgery, the animals had their respiratory movements recorded by video X-ray without any restraint...
February 23, 2018: Respiratory Physiology & Neurobiology
Huaide Liu, Jing Wang, Quanbin Zhang, Hong Zhang
Ten fucoidan (FPS) derivatives were successfully synthesized, and their potential neuroprotective and anticomplement activities were investigated employing various established in vitro systems. The aim of the present study was to investigate the effects of different substitute groups and molecular weights of fucoidan on neuroprotective and anticomplement activities. All FPS derivatives possessed considerable neuroprotective and anticomplement activities and had stronger activities than FPS in certain tests...
February 17, 2018: International Journal of Biological Macromolecules
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
Leonardo C Souza, Bruno J Martynhak, Taysa B Bassani, Joelle de M Turnes, Meira M Machado, Eric Moura, Roberto Andreatini, Maria A B F Vital
Parkinson's disease (PD) patients often suffer from circadian locomotor rhythms impairment and depression, important non-motor symptoms. It is known that toxin-based animal models of PD can reproduce these features. In a 6-hydroxydopamine (6-OHDA) intranigral model, we first investigated the possible disturbances on circadian rhythms of locomotor activity. The rats were divided into 6-OHDA and Sham groups. After a partial dopaminergic lesion, the 6-OHDA group showed slight alterations in different circadian locomotor rhythms parameters...
February 16, 2018: Physiology & Behavior
Xiaotong Zheng, Xuechai Chen, Minjun Guo, Sakhawat Ali, Yinghui Huang, Feiyi Sun, Kefu Liu, Zixuan Chen, Yulin Deng, Rugang Zhong
Salsolinol is an endogenous neurotoxin derived from dopamine, and has been proved to cause the apoptosis of the dopaminergic neurons involved in the pathogenesis of Parkinson's disease (PD). Salsolinol synthase is the key enzyme in the biosynthesis of salsolinol, and its activity exists in most regions of rat brain. However, the activity distribution and its catalyzed function in vivo are still unknown. On the basis of the chromatographic assay established previously, we investigated the activity of salsolinol synthase and salsolinol production in both cell and rat model of PD induced by 6-hydroxydopamine (6-OHDA)...
February 15, 2018: Neuroscience Letters
Rita Gálosi, Zoltán Petykó, Veronika Kállai, Attila Tóth, Tamás Ollmann, László Péczely, Anita Kovács, Beata Berta, László Lénárd
Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal cortex (mPFC) were examined on dopamine (DA) content and metabolism. 6-hydroxy-DOPA (6-OHDOPA) or 6-hydroxy-dopamine (6-OHDA) in combination with a potent DA reuptake inhibitor GBR 12935 or 6-OHDA were injected bilaterally into the mPFC in separate groups of animals. In addition, GBR 12935 or vehicle was injected into the mPFC in two other groups of animals as control experiments. NE and DA concentrations from postmortem tissue of the mPFC were measured using HPLC with electrochemical detection...
February 14, 2018: Behavioural Brain Research
Dana Mayer, Evelyn Kahl, Taygun C Uzuneser, Markus Fendt
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sunghee Estelle Park, Kang-Il Song, Hyungmin Kim, Seok Chung, Inchan Youn
Recent studies have established methods for establishing a rodent model that mimics progressive stages of human Parkinson's disease (PD), via injection of graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal pathway. However, the electrophysiological characteristics of the subthalamic nucleus (STN) in this model have not been fully elucidated in this model. This study aimed to investigate changes in the neuronal activity of the STN in a graded mouse model of PD. Increasing doses of 6-OHDA were unilaterally injected into the medial forebrain bundle (MFB) to produce a hemi-parkinsonian mouse model, mimicking early, moderate, advanced, and severe stages of human PD...
February 13, 2018: Behavioural Brain Research
Arianna Colini Baldeschi, Eugenia Pittaluga, Federica Andreola, Simona Rossi, Mauro Cozzolino, Giuseppe Nicotera, Gianluca Sferrazza, Pasquale Pierimarchi, Annalucia Serafino
In the last decades increasing evidence indicated a crucial role of the Wnt/β-catenin signaling in development of midbrain dopaminergic (mDA) neurons. Recently dysregulation of this pathway has been proposed as a novel pathomechanism leading to Parkinson's disease (PD) and some of the molecules participating to the signaling have been evaluated as potential therapeutic targets for PD. Atrial natriuretic peptide (ANP) is a cardiac-derived hormone having a critical role in cardiovascular homeostasis. ANP and its receptors (NPRs) are widely expressed in mammalian central nervous system (CNS) where they could be implicated in the regulation of neural development, synaptic transmission and information processing, as well as in neuroprotection...
2018: Frontiers in Aging Neuroscience
Joana Silva, Celso Alves, Susete Pinteus, Susana Mendes, Rui Pedrosa
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder of the central nervous system. Although the causes of PD pathogenesis remain incomplete, some evidences has suggested that oxidative stress is an important mediator in its pathogenesis. The aim of this study was to evaluate the protective effects of seaweeds with high antioxidant activity on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the human neuroblastoma cell line SH-SY5Y, as well as the associated intracellular signaling pathways...
February 14, 2018: BMC Complementary and Alternative Medicine
Xiaotian Sun, Pascaline Aimé, David Dai, Nagendran Ramalingam, John F Crary, Robert E Burke, Lloyd A Greene, Oren A Levy
Reduced function of parkin appears to be a central pathogenic event in Parkinson disease (PD). Increasing parkin levels enhances survival in models of PD-related neuronal death and is a promising therapeutic objective. Previously, we demonstrated that the transcription factor ATF4 promotes survival in response to PD-mimetic stressors by maintaining parkin levels. ATF4 translation is up-regulated by phosphorylation of the translation initiation factor eIF2α. The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes eIF2α dephosphorylation...
February 9, 2018: Experimental Neurology
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