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Kenyu Hayashi, Yu Hasegawa, Yushin Takemoto, Cheng Cao, Hiroto Takeya, Yoshihiro Komohara, Akitake Mukasa, Shokei Kim-Mitsuyama
Systemic organ dysfunction is one of the important issues for the patients with Alzheimer's disease (AD) and their caregivers. Recent evidences suggest that periodontitis is a possible risk factor for progression of AD and lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) which is a major periodontopathic bacteria induces cognitive impairment in mice. However, the precise relationships between the brain exposure of Pg-LPS and systemic organ dysfunction in AD patients are still undetermined. In this study, we investigated whether brain exposure of Pg-LPS induced systemic organ dysfunction in a model of AD mouse...
February 17, 2019: Experimental Gerontology
Johari Yap Abdullah, Zainul Ahmad Rajion, Arvind Gerard Martin, Azlan Jaafar, Abdul Rahman Izaini Ghani, Jafri Malin Abdullah
INTRODUCTION: Intracranial volume (ICV) is an important tool in the management of patients undergoing decompressive craniectomy (DC) surgery. The aim of this study was to validate ICV measurement applying the shape-based interpolation (SBI) method using open source software on computed tomography (CT) images. METHODS: The pre- and post-operative CT images of 55 patients undergoing DC surgery were analyzed. The ICV was measured by segmenting every slice of the CT images, and compared with estimated ICV calculated using the 1-in-10 sampling strategy and processed using the SBI method...
February 16, 2019: Neurocirugía
Marios Koutsakos, Patricia T Illing, Thi H O Nguyen, Nicole A Mifsud, Jeremy Chase Crawford, Simone Rizzetto, Auda A Eltahla, E Bridie Clemens, Sneha Sant, Brendon Y Chua, Chinn Yi Wong, E Kaitlynn Allen, Don Teng, Pradyot Dash, David F Boyd, Ludivine Grzelak, Weiguang Zeng, Aeron C Hurt, Ian Barr, Steve Rockman, David C Jackson, Tom C Kotsimbos, Allen C Cheng, Michael Richards, Glen P Westall, Thomas Loudovaris, Stuart I Mannering, Michael Elliott, Stuart G Tangye, Linda M Wakim, Jamie Rossjohn, Dhanasekaran Vijaykrishna, Fabio Luciani, Paul G Thomas, Stephanie Gras, Anthony W Purcell, Katherine Kedzierska
Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8+ T cells confer cross-protection against IAV strains, however the responses of CD8+ T cells to IBV and ICV are understudied. We investigated the breadth of CD8+ T cell cross-recognition and provide evidence of CD8+ T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8+ T cell epitopes from IBVs that were protective in mice and found memory CD8+ T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans...
February 18, 2019: Nature Immunology
Yusuke Kishimoto, Shingo Kasamatsu, Shuichi Yanai, Shogo Endo, Takaaki Akaike, Hideshi Ihara
We previously reported that 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins through S-guanylation. S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is a part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that regulates exocytosis. However, the biological relevance of 8-nitro-cGMP in the nervous system remains unclear...
February 14, 2019: Biochemical and Biophysical Research Communications
Jinxin Wang, Mara DePena, Graham Taylor, Elizabeth R Gilbert, Mark A Cline
Central administration of corticotropin-releasing factor (CRF), a 41-amino acid peptide, is associated with anorexigenic effects across various species, with particularly potent reductions in food intake in rodents and chickens (Gallus gallus domesticus), a species for which the most is known. The purpose of the current study was to determine the hypothalamic mechanism of CRF-induced anorexigenic effects in 7 day-old Japanese quail (Coturnix japonica), a less-intensely-selected gallinaceous relative to the chicken that can provide more evolutionary perspective...
February 12, 2019: General and Comparative Endocrinology
Vladimirs Pilipenko, Karina Narbute, Ines Amara, Angela Trovato, Maria Scuto, Jolanta Pupure, Baiba Jansone, Janis Poikans, Egils Bisenieks, Vija Klusa, Vittorio Calabrese
Neuroinflammation, oxidative stress, decreased glucose/energy metabolism, and disrupted neurotransmission are changes that occur early in sporadic Alzheimer's disease (AD), manifesting as mild cognitive impairment. Recently, the imbalanced function of the gamma-aminobutyric acid (GABA) system was identified as a critical factor in AD progression. Thus, maintaining balance among neurotransmitter systems, particularly the GABA system, can be considered a beneficial strategy to slow AD progression. The present study investigated the effects of the compound gammapyrone, a molecule containing three GABA moieties: "free" moiety attached to the position 4 of the 1,4-dihydropyridine (DHP) ring, and two "crypto" moieties as part of the DHP scaffold...
February 11, 2019: Journal of Neuroscience Research
Jinxin Wang, Justin Matias, Elizabeth R Gilbert, Tetsuya Tachibana, Mark A Cline
Central administration of corticotropin-releasing factor (CRF), a 41-amino acid peptide, is associated with potent anorexigenic effects in rodents and chickens. However, the mechanism underlying this effect remains unclear. Hence, the objective of the current study was to elucidate the hypothalamic mechanisms that mediate CRF-induced anorexia in 4 day-old Cobb-500 chicks. After intracerebroventricular (ICV) injection of 0.02 nmol of CRF, CRF-injected chicks ate less than vehicle chicks while no effect on water intake was observed at 30 min post-injection...
January 11, 2019: Neuropeptides
Koki Ogawa, Yuki Fuchigami, Masayori Hagimori, Shintaro Fumoto, Kazuo Maruyama, Shigeru Kawakami
AIM: Intracerebroventricular (ICV) administration of ultrasound-responsive bubbles and cranial ultrasound irradiation is reported as a transfection system for the cerebroventricular region. This study aimed to characterize the transfection system with respect to transfection efficiency, spatial distribution of transgene expression, and safety. METHODS: Plasmid DNA was transfected to mouse brain by ICV injection of ultrasound-responsive nanobubbles, followed by ultrasound irradiation to brain...
February 7, 2019: European Journal of Pharmaceutics and Biopharmaceutics
Siamak Shahidi, Nasrin Hashemi-Firouzi, Sara Soleimani Asl, Alireza Komaki
Alzheimer's disease (AD) is the most common cause of dementia, characterized by memory impairment and synaptic loss. Long-term potentiation (LTP), a type of synaptic plasticity, is impaired during AD. Serotonin type 6 receptor (5-HT6R) inactivation is proposed as a therapeutic target for AD. This study examined the effects of chronic administration of the 5-HT6R antagonist, SB-258585, on cognitive, memory, and hippocampal plasticity in a rat model of AD. Abeta neurotoxicity was induced in rats using Aβ (1...
February 5, 2019: Behavioural Brain Research
András Buzás, Péter Bokor, Beáta Balangó, Dávid Pintér, Miklós Palotai, Balázs Simon, Krisztina Csabafi, Gyula Telegdy, Gyula Szabó, Zsolt Bagosi
The aim of the present study was to investigate the participation of corticotropin-releasing factor (CRF) receptors (CRF1 and CRF2) in the alterations of the dorsal and ventral striatal dopamine release and the vertical and horizontal locomotor activity observed in rats following chronic nicotine treatment and consequent acute withdrawal. In this purpose, male Wistar rats were exposed to repeated intraperitoneal (ip) injection with nicotine or saline solution for 7 days. On the 8th day or the 9th day the rats were injected intracerebroventricularly (icv) with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B or saline solution...
March 1, 2019: Brain Research
Tymoteusz Żera, Artur Nowiński, Agnieszka Segiet, Paweł Smykiewicz
High salt diet alters cardiovascular control by increasing concentration of sodium ions (Na+ ) in cerebrospinal fluid (CSF) and is a risk factor for hypertension. Hypernatremic conditions activate microglia and upregulate renin-angiotensin system in the brain. Thus, we checked if chronic elevation of CSF Na+ affects neural control of circulatory system via microglia and brain angiotensin type 1 receptors (AT1Rs). Normotensive adult male Sprague-Dawley rats received two-week intracerebroventricular (ICV) infusion of either isoosmotic saline (0...
January 6, 2019: Autonomic Neuroscience: Basic & Clinical
Tingxu Yan, Bosai He, Mengjie Xu, Bo Wu, Feng Xiao, Kaishun Bi, Ying Jia
Kaempferide (KF) is a compound of flavonoids from Alpinae oxyphylla Miq, and the herb itself is used as a classical tonic agent. This paper aims to investigate the effects of KF on cognitive function impairment and neurodegeneration in the mouse model of Alzheimer's disease induced by intracerebroventricular (ICV) injection of Aβ1-42 . The mice were treated with KF at doses of 0.02 and 0.2 mg/kg/day (ICV) for five consecutive days after Aβ1-42 exposures. The behavioral test results showed that KF could prevent cognitive decline in mice induced by Aβ1-42 as assessed by the locomotor activity test, Y-maze test, and Morris water maze test...
January 30, 2019: Phytotherapy Research: PTR
Gokhan Arslan, Bahattin Avci, Süleyman Emre Kocacan, Emil Rzayev, Mustafa Ayyildiz, Erdal Agar
Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels play in the effect of P2X7Rs on penicillin-induced epileptiform activity. In the first set of experiments, P2X7R agonist BzATP (at 25-, 50-, 100- and 200-μg doses), P2X7R antagonist A-438079 (at 5-, 10-, 20- and 40-μg doses) and T-type calcium ion channel antagonist NNC-550396, were administered for electrophysiological analyses 30 min after penicillin injection (2...
January 26, 2019: Neuropharmacology
M Demir, U Yilmaz, C Colak, Y Cigremis, F Ozyalin, I Tekedereli, S Sandal
Alzheimer's disease (AD) is a progressive neurodegenerative disease. This study was performed to determine the possible relationship between melatonin, which is known to play a role in the neuro-protective mechanism in AD, and fasciculation and elongation protein zeta 1 (FEZ1). Thirty male rats were included and separated into 3 groups (n = 10) as vehicle (artificial cerebrospinal fluid), streptozotocin (STZ) and STZ+melatonin (MLT). Two intracerebroventricular (icv) injections of 3 mg/kg STZ were made 48 hours apart...
2019: Bratislavské Lekárske Listy
Simin Afshar, Siamak Shahidi, Ali Haeri Rohani, Sara Soleimani Asl, Alireza Komaki
Alzheimer's disease (AD) is a neurodegenerative disorder and neuropathologically characterized by the aggregation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, enhanced oxidative stress and neurodegeneration. Involvement of serotonergic systems in AD has been supposed and it is suggested that serotonin receptors modulation may provide a novel therapeutic target for AD. This study aimed at investigating the protective effect of NAD-299 (the selective 5-HT1A receptor antagonist) and TCB-2 (the potent5-HT2A receptor agonist) on the hippocampal oxidative stress biomarkers and the number of intact neurons in streptozotocin (STZ)-induced Alzheimer's disease in rats...
January 23, 2019: Journal of Chemical Neuroanatomy
Claudia Cristiano, Floriana Volpicelli, Pellegrino Lippiello, Benedetta Buono, Federica Raucci, Marialuisa Piccolo, Asif Jilani Iqbal, Carlo Irace, Maria Concetta Miniaci, Carla Perrone Capano, Antonio Calignano, Nicola Mascolo, Francesco Maione
BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of T helper 17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies, however the role of the main cytokine, IL-17, has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by intracerebroventricular (ICV) or intranasal (IN) routes on amyloid-β-induced neuroinflammation and memory impairment in mice...
January 23, 2019: British Journal of Pharmacology
Elisa R Torres, Siobhan M Hoscheidt, Barbara B Bendlin, Vincent A Magnotta, Gabriel D Lancaster, Roger L Brown, Sergio Paradiso
BACKGROUND: White matter hyperintensities (WMH) observed on magnetic resonance images are associated with depression and increase risk of stroke, dementia and death. The association between physical activity and WMH has been inconsistently reported in the literature, perhaps because studies did not account for a lifetime of physical activity or depression. OBJECTIVES: To determine the extent to which a lifetime of leisure-time physical activity is associated with less WMH while accounting for depression...
January 21, 2019: Nursing Research
Nayara S S Aquino, Ilona C Kokay, Carolina Thörn Perez, Sharon R Ladyman, Patricia C Henriques, Juneo F Silva, Christian Broberger, David R Grattan, Raphael E Szawka
Kisspeptin has been shown to stimulate prolactin secretion. We investigated whether kisspeptin acts through the Kiss1 receptor (Kiss1r) to regulate dopamine and prolactin. Initially, we evaluated prolactin response in Kiss1r-deficient mouse line, in which Kiss1r has been knocked into gonadotrophin-releasing hormone (GnRH) neurons (Kiss1r-/-R). Intracerebroventricular (icv) kisspeptin-10 (Kp-10) increased prolactin release in wild-type but not in Kiss1r-/-R female mice. In ovariectomized, estradiol-treated (OVX+E2) rats, the Kiss1r antagonist, kisspeptin-234, abolished the Kp-10-induced increase in prolactin release but failed to prevent the concomitant reduction in the activity of tuberoinfundibular dopaminergic (TIDA) neurons, as determined by the 3,4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence...
January 21, 2019: Endocrinology
Lewis Haddow, Carole Helene Sudre, Magdalena Sokolska, Richard Cary Gilson, Ian Williams, Xavier Golay, Sebastien Ourselin, Alan Winston, Caroline A Sabin, Jorge Cardoso, Rolf Jäger
We assessed whether HIV status was associated with white matter hyperintensities (WMH), a neuroimaging correlate of cerebral small vessel disease, in men aged ≥50 years. A cross-sectional substudy was nested within a larger cohort study. Virologically suppressed men living with HIV (MLWH) and demographically matched HIV negative men aged ≥50 underwent magnetic resonance imaging (MRI) at 3 Tesla. Sequences included volumetric 3D T1-weighted, FLAIR and pseudocontinuous arterial spin labelling. Regional segmentation by automated image processing algorithms was used to extract WMH volume (WMHV) and resting cerebral blood flow (CBF)...
January 22, 2019: AIDS Research and Human Retroviruses
Simon Haworth, Chin Yang Shapland, Caroline Hayward, Bram P Prins, Janine F Felix, Carolina Medina-Gomez, Fernando Rivadeneira, Carol Wang, Tarunveer S Ahluwalia, Martine Vrijheid, Mònica Guxens, Jordi Sunyer, Ioanna Tachmazidou, Klaudia Walter, Valentina Iotchkova, Andrew Jackson, Louise Cleal, Jennifer Huffmann, Josine L Min, Lærke Sass, Paul R H J Timmers, George Davey Smith, Simon E Fisher, James F Wilson, Tim J Cole, Dietmar Fernandez-Orth, Klaus Bønnelykke, Hans Bisgaard, Craig E Pennell, Vincent W V Jaddoe, George Dedoussis, Nicholas Timpson, Eleftheria Zeggini, Veronique Vitart, Beate St Pourcain
Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV...
January 21, 2019: Nature Communications
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