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Changyoun Kim, Brian Spencer, Edward Rockenstein, Hodaka Yamakado, Michael Mante, Anthony Adame, Jerel Adam Fields, Deborah Masliah, Michiyo Iba, He-Jin Lee, Robert A Rissman, Seung-Jae Lee, Eliezer Masliah
BACKGROUND: Synucleinopathies of the aging population are an heterogeneous group of neurological disorders that includes Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and are characterized by the progressive accumulation of α-synuclein in neuronal and glial cells. Toll-like receptor 2 (TLR2), a pattern recognition immune receptor, has been implicated in the pathogenesis of synucleinopathies because TLR2 is elevated in the brains of patients with PD and TLR2 is a mediator of the neurotoxic and pro-inflammatory effects of extracellular α-synuclein aggregates...
August 9, 2018: Molecular Neurodegeneration
Roman Tashev, Margarita Ivanova
BACKGROUND: Accumulated evidence suggests that the enhanced brain angiotensin II (Ang II) activity is associated with stress and anxiety. More recent reports demonstrated that Ang II function is elevated in depression, but the role of hippocampal Ang II and its receptors in this state is not well established. The present study investigated the effects of Ang II and losartan (a selective Аng II type 1 receptor antagonist) microinjected into the hippocampal CA1 area on the anxiety-like behavior in rats with a model of depression...
March 8, 2018: Pharmacological Reports: PR
Hongjie Wu, Jing Li, Dongxiao Xu, Qiansheng Zhang, Tao Cui
The aim of this study was to investigate the therapeutic effect of growth differentiation factor 5 (GDF-5) on traumatic brain injury (TBI) in mice. We utilized a controlled cortical impact to establish a mouse TBI model, and then stereotaxically administered 25 or 100 ng GDF-5 into the bilateral hippocampal dentate gyrus (DG) of each of the animals. Seven days after the injury, some of the animals were sacrificed for immunohistochemical and immunofluorescence examination of 5-bromo-2'-deoxyuridine (BrdU), Sox-2, doublecortin (DCX) and phosphorylated cAMP response element binding protein (p-CREB)...
2018: Frontiers in Neurology
Thomas G Schuhmann, Tao Zhou, Guosong Hong, Jung Min Lee, Tian-Ming Fu, Hong-Gyu Park, Charles M Lieber
Implantable brain electrophysiology probes are valuable tools in neuroscience due to their ability to record neural activity with high spatiotemporal resolution from shallow and deep brain regions. Their use has been hindered, however, by mechanical and structural mismatches between the probes and brain tissue that commonly lead to micromotion and gliosis with resulting signal instability in chronic recording experiments. In contrast, following the implantation of ultraflexible mesh electronics via syringe injection, the mesh probes form a seamless, gliosis-free interface with the surrounding brain tissue that enables stable tracking of individual neurons on at least a year timescale...
July 21, 2018: Journal of Visualized Experiments: JoVE
Nihan Çarçak, Melis Yavuz, Tuğba Eryiğit Karamahmutoğlu, Akif Hakan Kurt, Meral Urhan Küçük, Filiz Yılmaz Onat, Kansu Büyükafsar
Rho/Rho-kinase (ROCK) signaling contributes to neuroinflammation, epileptogenesis, and seizures in convulsive-type epilepsies. However, this pathway has not been investigated in absence epilepsy. We investigated RhoA activity in genetic absence epilepsy rats from Strasburg (GAERS) and the effects of ROCK inhibitors Y-27632 and fasudil on spike-and-wave discharges (SWDs) of GAERS. ROCK level and activity were measured by Western blot analysis in the brain areas involved in absence seizures (i.e., cortex and thalamus) and hippocampus...
August 2, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Lei Wang, Zi Wang, Jiandang Shi, Qian Jiang, Hong Wang, Xu Li, Di Hao
The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) protects a variety of cell types against neuronal apoptosis by binding to apolipoprotein E receptor 2 (ApoER2). The present study aimed to determine the association between PCSK9/ApoER2 signaling and neuronal apoptosis following middle cerebral artery occlusion (MCAO) injury in hyperlipidemic mice. For this purpose, C57BL/6 mice fed with a high‑fat diet (HFD) for 6 weeks were exposed to MCAO. Subsequently, PCSK9 was inhibited by a lentiviral vector harboring short‑hairpin RNA (shRNA) targeting PCSK9, which was stereotaxically injected into the cerebral cortex of mice...
July 31, 2018: International Journal of Molecular Medicine
Kilian Fröhlich, Klemens Winder, Ralf A Linker, Konstantin Huhn, Tobias Engelhorn, Arnd Dörfler, De-Hyung Lee, Stefan Schwab, Frank Seifert
Secondary paroxysmal dyskinesia is a rare but life-quality-compromising symptom in multiple sclerosis (MS) and might be associated with particular MS lesions. The present study intended to determine associations between paroxysmal dyskinesia and the MS-associated lesion site using a voxelwise lesion analysis. We conducted a retrospective study and sought MS patients with documented paroxysmal dyskinesia and controls without paroxysmal dyskinesia matched for age, disease severity, and disease duration in a local database...
July 31, 2018: Journal of Neurology
Shih-Yun Chen, Hsiao-Ying Kuo, Fu-Chin Liu
Many genes are expressed in embryonic brains, and some of them are continuously expressed in the brain after birth. For such persistently expressed genes, they may function to regulate the developmental process and/or physiological function in neonatal brains. To investigate neurobiological functions of specific genes in the brain, it is essential to inactivate genes in the brain. Here, we describe a simple stereotaxic method to inactivate gene expression in the striatum of transgenic mice at neonatal time windows...
July 10, 2018: Journal of Visualized Experiments: JoVE
Simoneide Souza Titze de Almeida, Camila Hillesheim Horst, Cristina Soto-Sánchez, Eduardo Fernandez, Ricardo Titze de Almeida
MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level by triggering RNA interference. In such a sense, aberrant expressions of miRNAs play critical roles in the pathogenesis of many disorders, including Parkinson's disease (PD). Controlling the level of specific miRNAs in the brain is thus a promising therapeutic strategy for neuroprotection. A fundamental need for miRNA regulation (either replacing or inhibition) is a carrier capable of delivering oligonucleotides into brain cells. This study aimed to examine a polymeric magnetic particle, Neuromag® , for delivery of synthetic miRNA inhibitors in the rat central nervous system...
July 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kengo Setta, Daigo Kojima, Yasuyoshi Shimada, Jun Yoshida, Sotaro Oshida, Kentaro Fujimoto, Shouta Tsutsui, Takayuki Chiba, Shunrou Fujiwara, Kazunori Terasaki, Kuniaki Ogasawara
OBJECTIVE: The purpose of the present study was to determine how accurately relative cerebral blood flow (RCBF) and relative cerebrovascular reactivity (RCVR) to acetazolamide assessed using brain perfusion single-photon emission computed tomography (SPECT) detected misery perfusion identified on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). METHODS: Oxygen extraction fraction (OEF), RCBF, and RCVR were assessed using 15 O gas PET and N-isopropyl-p-[123 I]-iodoamphetamine SPECT without and with acetazolamide challenge, respectively, in 45 patients...
July 20, 2018: Annals of Nuclear Medicine
Gustavo C Dal-Pont, Wilson R Resende, Roger B Varela, Samira Menegas, Kerolen S Trajano, Bruna R Peterle, João Quevedo, Samira S Valvassori
The present study evaluated the effects of AR-A014418 on behavioral and oxidative stress parameters of rats submitted to the animal model of mania induced by ouabain (OUA). Wistar rats were submitted to stereotaxic surgery and received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid (aCSF), OUA, or AR-A014418. After 7 days, the animals were submitted to open-field test. After behavioral analysis, the brains were dissected in frontal cortex and hippocampus to the evaluation of oxidative stress...
July 20, 2018: Molecular Neurobiology
Elham Hoveizi, Tayebeh Mohammadi, Ahmad Ali Moazedi, Nastaran Zamani, Azade Eskandary
BACKGROUND AIMS: Degeneration of the central nerve system, particularly in Alzheimer's disease, is a burden on society, and despite years of research, there is no effective treatment. Cell therapy appears to be an option that is of growing interest in neural studies. The main aim of this study was to investigate the histological and physiological effects of transplantation the neuron-like cell (NLC)-derived mouse embryonic stem cells (mESCs) on the repair of brain lesions in an Alzheimer's animal model (AM) in rats...
July 16, 2018: Cytotherapy
Laura Liñares-Pose, Eva Rial-Pensado, Ánxela Estévez-Salguero, Edward Milbank, Ismael González-García, Claudia Rodríguez, Patricia Seoane-Collazo, Noelia Martinez-Sánchez, Rubén Nogueiras, Dolores Prieto, Carlos Diéguez, Cristina Contreras, Miguel López
Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic treatment with adenoviruses harboring GRP78 in the VMH reduced hypothalamic endoplasmic reticulum ER stress and reversed vHFD-induced obesity...
July 17, 2018: Genes
Jonathan Palma, Madhusudhanan Narasimhan, Josée Guindon, Khalid Benamar
The growing therapeutic use (self-medication) of cannabinoids by HIV-1 infected people and the recent interest in the possible medicinal use of cannabinoids, particularly in pain management, create an urgent need to identify their potential interactions with HIV-1. The goal here is to determine any interaction between proteins of HIV-1 and the analgesic effectiveness of cannabinoid at supraspinal level. Young adult male rats (Sprague-Dawley) were stereotaxically pretreated with HIV-1 envelope glycoprotein 120 (gp120) into the periaqueductal gray (PAG) area, the primary control center of pain modulation...
July 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Khayelihle B Makhathini, Oualid Abboussi, Musa V Mabandla, William M U Daniels
Human immunodeficiency virus type 1 (HIV-1) affects the central nervous system (CNS) that may lead to the development of HIV-associated neuropathologies. Tat protein is one of the viral proteins that have been linked to the neurotoxic effects of HIV. Since many individuals living with HIV often experience significant adverse circumstances, the present study investigated whether exposure to stressful conditions would exacerbate harmful effects of tat protein on brain function. Tat protein (10 μg/10 μl) was injected bilaterally into the dorsal hippocampus of the animal using stereotaxic techniques...
July 10, 2018: Metabolic Brain Disease
Hiviny de Ataides Raquel, Nathalia Zerbinatti Ferreira, Bruno Fernando Cruz Lucchetti, Bárbara Falquetto, Phileno Pinge-Filho, Lisete Compagno Michelini, Marli Cardoso Martins-Pinge
Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p...
July 3, 2018: Nitric Oxide: Biology and Chemistry
Hanson Ho, Matt De Both, Ashley Siniard, Sasha Sharma, James H Notwell, Michelle Wallace, Dino P Leone, Amy Nguyen, Eric Zhao, Hannah Lee, Daniel Zwilling, Kimberly R Thompson, Steven P Braithwaite, Matthew Huentelman, Thomas Portmann
Recent advances in single-cell technologies are paving the way to a comprehensive understanding of the cellular complexity in the brain. Protocols for single-cell transcriptomics combine a variety of sophisticated methods for the purpose of isolating the heavily interconnected and heterogeneous neuronal cell types in a relatively intact and healthy state. The emphasis of single-cell transcriptome studies has thus far been on comparing library generation and sequencing techniques that enable measurement of the minute amounts of starting material from a single cell...
2018: Frontiers in Cellular Neuroscience
Pengfei Yang, Zhenzhen Wang, Zhao Zhang, Dandan Liu, Emmanuel Nicholas Manolios, Chen Chen, Xu Yan, Wei Zuo, Naihong Chen
BACKGROUND: Stereotaxic procedures in rats are frequently used in neurological research. The commonly used rat brain stereotaxic atlases areThe Rat Brain in Stereotaxic Coordinates, the second most cited book in science, and Stereotaxic Atlas of Rat Brain (in Chinese) which based on Wistar rats of 290 g and SD rats of 225 g, respectively. However, rats of different weight are frequently used, while the stereotaxic coordinates of their brain regions show obvious differences with the rats on which the atlases were based...
June 28, 2018: Journal of Neuroscience Methods
Joana M Gaspar, Natália Ferreira Mendes, Felipe Corrêa-da-Silva, José C de Lima-Junior, Rodrigo C Gaspar, Eduardo R Ropelle, Eliana P Araujo, Humberto M Carvalho, Lício A Velloso
Hypothalamic hypoxia-inducible factor-1 (HIF-1) can regulate whole-body energy homeostasis in response to changes in blood glucose, suggesting that it acts as a sensor for systemic energy stores. Here, we hypothesized that hypothalamic HIF-1 could be affected by diet-induced obesity (DIO). We used eight-week old, male C57Bl6 mice, fed normal chow diet or with high fat diet for 1, 3, 7, 14 and 28 days. The expression of HIF-1alpha and HIF-1beta was measured by PCR and western blotting and its hypothalamic distribution was evaluated by fluorescence microscopy...
June 21, 2018: Brain, Behavior, and Immunity
Emidio Beraldo Neto, Douglas O C Mariano, Lucas A Freitas, Ana L C Dorce, Adriana N Martins, Daniel C Pimenta, Fernanda C V Portaro, Daniela Cajado-Carvalho, Valquiria A C Dorce, Ana L A Nencioni
Scorpion venoms are composed of several substances with different pharmacological activities. Neurotoxins exert their effects by targeting ion channels resulting in toxic effects to mammals, insects and crustaceans. Tb II-I, a fraction isolated from Tityus bahiensis scorpion venom, was investigated for its ability to induce neurological and immune-inflammatory effects. Two putative β-sodium channel toxins were identified in this fraction, Tb2 II and Tb 4, the latter having been completely sequenced by mass spectrometry...
June 19, 2018: Toxins
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