The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK (2016) Neuropharmacology, 101, pp. 426-438. Cited 1 time. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945555258&partnerID=40&md5=a270d224a8d0453816b233f15e36d21a DOI: 10.1016/j.neuropharm.2015.10.019 AFFILIATIONS: aDepartment of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, Naples, Italy; bDepartment of Neuroscience, University of Torino, Torino, Italy; cNeuroscience Institute Cavalieri Ottolenghi (NICO), Torino, Italy; dInstitute of Genetics and Biophysics adriano Buzzati Traverso, CNR, Naples, Italy; eDepartment of Pharmacy - Drug Science, University of Bari a. Moro, Italy ABSTRACT: The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum. © 2015 Elsevier Ltd. All rights reserved. AUTHOR KEYWORDS: 5-HT7 receptor; Cerebellum; Long-term depression; Purkinje cell; Serotonin; Synaptic transmission DOCUMENT TYPE: Article
domenica 26 giugno 2016
Lippiello, P.a , Hoxha, E.b c , Speranza, L.d , Volpicelli, F.a d , Ferraro, A.a , Leopoldo, M.e , Lacivita, E.e , Perrone-Capano, C.a d , Tempia, F.b c , Miniaci, M.C.a
Vacca, M.a , Tripathi, K.P.b , Speranza, L.a , Aiese Cigliano, R.c , Scalabrì, F.d , Marracino, F.d , Madonna, M.d , Sanseverino, W.c , Perrone-Capano, C.a e , Guarracino, M.R.b , D'Esposito, M.a d Effects of Mecp2 loss of function in embryonic cortical neurons: A bioinformatics strategy to sort out non-neuronal cells variability from transcriptome profiling (2016) BMC Bioinformatics, . Article in Press. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84954458478&partnerID=40&md5=dc50fc13e2396f6d2c43a5c8b65e54f7 DOI: 10.1186/s12859-015-0859-7 AFFILIATIONS: aInstitute of Genetics and Biophysics A. Buzzati Traverso, National Research Council (CNR)-80131, Naples; bLaboratory for Genomics, Transcriptomics and Proteomics (LAB-GTP), High Performance Computing and Networking Institute (ICAR), National Research Council (CNR)-80131, Naples; cSequentia Biotech SL, Calle Comte D'Urgell, Barcelona, 240 08036; dIRCCS Neuromed, via dell'Elettronica, Pozzilli (Is); eDepartment of Pharmacy, University of Naples Federico II, Naples ABSTRACT: Background: Mecp2 null mice model Rett syndrome (RTT) a human neurological disorder affecting females after apparent normal pre- and peri-natal developmental periods. Neuroanatomical studies in cerebral cortex of RTT mouse models revealed delayed maturation of neuronal morphology and autonomous as well as non-cell autonomous reduction in dendritic complexity of postnatal cortical neurons. However, both morphometric parameters and high-resolution expression profile of cortical neurons at embryonic developmental stage have not yet been studied. Here we address these topics by using embryonic neuronal primary cultures from Mecp2 loss of function mouse model. Results: We show that embryonic primary cortical neurons of Mecp2 null mice display reduced neurite complexity possibly reflecting transcriptional changes. We used RNA-sequencing coupled with a bioinformatics comparative approach to identify and remove the contribution of variable and hard to quantify non-neuronal brain cells present in our in vitro cell cultures. Conclusions: Our results support the need to investigate both Mecp2 morphological as well as molecular effect in neurons since prenatal developmental stage, long time before onset of Rett symptoms. © 2015 Vacca et al. AUTHOR KEYWORDS: Embryonic cortical neurons; MeCP2; Neural cells; Primary branching; Rett syndrome; RNA-sequencing DOCUMENT TYPE: Article in Press
Niola, M.a , Musella, C.b , Paciello, L.a , Siani, P.c , Paternoster, M.a , Di Lorenzo, P.a Abusive head trauma: Aspetti clinici e medico-legali (2016) Quaderni ACP, 23 (3), pp. 119-123. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973926545&partnerID=40&md5=c2bea19083f026b9f22345045f7b111e AFFILIATIONS: Dipartimento di Scienze Biomediche Avanzate, Cattedra di Medicina Legale, Università degli Studi di Napoli “Federico II”, Italy; Direttore della Struttura Complessa di Medicina Legale, AORN “Santobono-Pausilipon”, Napoli, Italy; Direttore della Struttura Complessa di Pediatria, AORN “Santobono-Pausilipon”, Napoli, Italy ABSTRACT: The not uncommon occurrence of Abusive Head Trauma (AHT) together with the difficulties in diagnosis, the risk of recurrence of violent conduct as well as the important neurological sequelae make it appropriate to conduct extensive cognitive studies aimed at identifying the clinical and instrumental criteria useful for the diagnosis of the aforementioned abuse syndrome. Approximately 30-50% of shaken children present, as sequelae of brain trauma, major neurological and cognitive deficits; from 7 to 30% die from the consequences associated with AHT. The diagnosis of AHT is difficult to formulate because frequently there is no external injury and there are no specific symptoms, so a differential diagnosis with other pathological aspects is necessary. The Authors seek to promote a more widespread knowledge of the clinical signs that characterize this syndrome, as well as to establish guidelines to facilitate diagnosis. © 2016, Associazione Culturale Pediatri. All rights reserved. DOCUMENT TYPE: Article
Iovino, M.a , Iovine, N.a , Mondillo, F.b , Guastamacchia, E.c , Licchelli, B.c , Giagulli, V.A.c , Triggiani, V.c Hypopituitarism in neurocritical patients: A case report (2016) Endocrine, Metabolic and Immune Disorders - Drug Targets, 16 (1), pp. 28-31. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973644414&partnerID=40&md5=9e531b9718b69ac561a1e918dceacc21 AFFILIATIONS: aEndocrinology and Metabolic Diseases, Eboli Hospital, Salerno, Italy; bRadiology, Eboli Hospital, Salerno, Italy; cEndocrinology and Metabolic Diseases, Interdisciplinary Department of Medicine, University of Bari, Bari, Italy ABSTRACT: Background: Besides changes in pituitary hormones secretion observed during the acute phase of stroke as an adaptive response to injury or an effect of drugs, a true hypopituitarism due to ischemic and/or hemorrhagic damage at the hypothalamus and/or pituitary gland can develop after a stroke. Case Report: We report a case of a 72-year-old woman showing clinical signs and laboratory data suggesting a secondary adrenal insufficiency following a recent acute brain ischemia. Cortisone therapy significantly improved this pituitary dysfunction. Conclusions: Clinicians must pay attention to the hypothalamic-pituitary axis in neurocritical patients because hormonal replacement therapy may be life-saving. © 2016 Bentham Science Publishers. AUTHOR KEYWORDS: Adrenal insufficiency; Hyponatremia; Hypopituitarism; Neuro-critical patients DOCUMENT TYPE: Article
Davinelli, S.a , Maes, M.b c , Corbi, G.a , Zarrelli, A.d , Willcox, D.C.e f , Scapagnini, G.a Dietary phytochemicals and neuro-inflammaging: From mechanistic insights to translational challenges (2016) Immunity and Ageing, 13 (1), art. no. 16, . Cited 1 time. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973872520&partnerID=40&md5=577765246162937693bc4b9bb030a252 DOI: 10.1186/s12979-016-0070-3 AFFILIATIONS: aUniversity of Molise, Department of Medicine and Health Sciences, School of Medicine, Campobasso, Italy; bDeakin University, IMPACT Research Center, Geelong, Australia; cChulalongkorn University, Department of Psychiatry, Faculty of Medicine, Bangkok, Thailand; dUniversity of Naples Federico II, Complesso Universitario Monte S. Angelo, Department of Chemical Sciences, Naples, Italy; eOkinawa International University, Department of Human Welfare, Okinawa, Japan; fJohn A. Burns School of Medicine, University of Hawaii, Department of Geriatric Medicine, Honolulu, United States ABSTRACT: An extensive literature describes the positive impact of dietary phytochemicals on overall health and longevity. Dietary phytochemicals include a large group of non-nutrients compounds from a wide range of plant-derived foods and chemical classes. Over the last decade, remarkable progress has been made to realize that oxidative and nitrosative stress (O&NS) and chronic, low-grade inflammation are major risk factors underlying brain aging. Accumulated data strongly suggest that phytochemicals from fruits, vegetables, herbs, and spices may exert relevant negative immunoregulatory, and/or anti-O&NS activities in the context of brain aging. Despite the translational gap between basic and clinical research, the current understanding of the molecular interactions between phytochemicals and immune-inflammatory and O&NS (IO&NS) pathways could help in designing effective nutritional strategies to delay brain aging and improve cognitive function. This review attempts to summarise recent evidence indicating that specific phytochemicals may act as positive modulators of IO&NS pathways by attenuating pro-inflammatory pathways associated with the age-related redox imbalance that occurs in brain aging. We will also discuss the need to initiate long-term nutrition intervention studies in healthy subjects. Hence, we will highlight crucial aspects that require further study to determine effective physiological concentrations and explore the real impact of dietary phytochemicals in preserving brain health before the onset of symptoms leading to cognitive decline and inflammatory neurodegeneration. © 2016 Davinelli et al. AUTHOR KEYWORDS: Aging; Brain; Diet; Inflammation; Oxidative stress; Phytochemicals DOCUMENT TYPE: Review
Signoriello, E.a , Lanzillo, R.b , Brescia Morra, V.b , Di Iorio, G.a , Fratta, M.a , Carotenuto, A.b , Lus, G.a Lymphocytosis as a response biomarker of natalizumab therapeutic efficacy in multiple sclerosis (2016) Multiple Sclerosis, 22 (7), pp. 921-925. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973455035&partnerID=40&md5=b9ac703c0418eba67b06124f01293f1b DOI: 10.1177/1352458515604381 AFFILIATIONS: aMultiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, via Pansini 5, Naples, Italy; bDepartment of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University-School of Medicine, Italy ABSTRACT: Background: Natalizumab is an effective therapy in relapsing-remitting multiple sclerosis (RRMS), as it reduces lymphocyte transmigration through the blood-brain barrier (BBB) and induces lymphocytosis. Objectives: To analyse natalizumab-induced lymphocytosis (NIL) as a biomarker of drug efficacy. Materials and methods: We enrolled 50 relapsing-remitting (RR) and progressive-relapsing (PR) natalizumab-treated patients who had received at least 16 infusions and had been tested for lymphocyte count 24 hours before each administration. Clinical, MRI and hematological data were collected. Patients were divided into responders and sub-optimal responders according to the experience of at least one clinical and/or instrumental relapse during the treatment. Results: In 15 (30%) patients, an instrumental/clinical (14) or only instrumental (one) relapse occurred. We found a statistically significant difference in the mean percentage of the lymphocytes between the two groups over the first ten administrations (p=0.04). The comparison between the time-to-relapse in the groups with high and low levels of lymphocytes showed that the group with a low NIL had a greater risk of relapse (p=0.03). Conclusions: We suggest that NIL could be a biomarker of therapeutic efficacy in patients with RRMS treated with natalizumab, and that the risk of relapse may be higher in patients with a lower-than-expected NIL. © SAGE Publications. AUTHOR KEYWORDS: Biomarkers; multiple sclerosis; Natalizumab DOCUMENT TYPE: Article
mercoledì 22 giugno 2016
Di Porzio, U.
The brain from within
(2016) Frontiers in Human Neuroscience, 10 (JUNE2016), art. no. 265, . https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973294686&partnerID=40&md5=169d8305711624551776d99e1a5f6251 DOI: 10.3389/fnhum.2016.00265 AFFILIATIONS: Institute of Genetics and Biophysics “A. Buzzati-Traverso”, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy
ABSTRACT: Functional magnetic resonance imaging (fMRI) provides a powerful way to visualize brain functions and observe brain activity in response to tasks or thoughts. It allows displaying brain damages that can be quantified and linked to neurobehavioral deficits. fMRI can potentially draw a new cartography of brain functional areas, allow us to understand aspects of brain function evolution or even breach the wall into cognition and consciousness. However, fMRI is not deprived of pitfalls, such as limitation in spatial resolution, poor reproducibility, different time scales of fMRI measurements and neuron action potentials, low statistical values. Thus, caution is needed in the assessment of fMRI results and conclusions. Additional diagnostic techniques based on MRI such as arterial spin labeling (ASL) and the measurement of diffusion tensor imaging (DTI) provide new tools to assess normal brain development or disruption of anatomical networks in diseases. A cutting edge of recent research uses fMRI techniques to establish a “map” of neural connections in the brain, or “connectome”. It will help to develop a map of neural connections and thus understand the operation of the network. New applications combining fMRI and real time visualization of one’s own brain activity (rtfMRI) could empower individuals to modify brain response and thus could enable researchers or institutions to intervene in the modification of an individual behavior. The latter in particular, as well as the concern about the confidentiality and storage of sensitive information or fMRI and lie detectors forensic use, raises new ethical questions. © 2016 di Porzio. AUTHOR KEYWORDS: ASL; DTI; Ethical issues; FMRI; Neurofeedback; Neuroimaging; Neuroplasticity; RtfMRI DOCUMENT TYPE: Review
Tillema, J.M.a b , Hulst, H.E.c , Rocca, M.A.d e , Vrenken, H.f g , Steenwijk, M.D.a , Damjanovic, D.d , Enzinger, C.h i j , Ropele, S.h i j , Tedeschi, G.k l m , Gallo, A.k l m , Ciccarelli, O.n o , Rovira, A.p q , Montalban, X.q , De Stefano, N.r , Stromillo, M.L.r , Filippi, M.d e , Barkhof, F.a Regional cortical thinning in multiple sclerosis and its relation with cognitive impairment: A multicenter study (2016) Multiple Sclerosis, 22 (7), pp. 901-909. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973449787&partnerID=40&md5=b697f04f78d6bd745bb785e104b0b4b6 DOI: 10.1177/1352458515607650 AFFILIATIONS: Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Netherlands; Department of Neurology, Mayo Clinic, United States; Department of Anatomy and Neurosciences, VU University Medical Center, Netherlands; Neuroimaging Research Unit, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy; Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy; Department of Radiology and Nuclear Medicine, VU University Medical Center, Netherlands; Department of Physics and Medical Technology, VU University Medical Center, Netherlands; Department of Neurology, Medical University of Graz, Austria; Division of Neuroradiology, Medical University of Graz, Austria; Department of Radiology, Medical University of Graz, Austria; k)MRI Center SUN-FISM, Second University of Naples, Italy; l)Institute of Diagnosis and Care Hermitage-Capodimonte, Italy; m)Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, United Kingdom; National Institute for Health Research (NIHR), University College London Hospital (UCLH), Biomedical Research Centre (BRC), United Kingdom; Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Spain; Unitat de Neuroimmunologia Clinica, CEM-Cat, Hospital Universitari Vall d'Hebron, Spain; Department of Medicine, Surgery and Neurosciences, University of Siena, Italy ABSTRACT: Objectives: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing-remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance. Methods: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups. Results: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning. Conclusions: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains. © SAGE Publications. AUTHOR KEYWORDS: cognitive impairment; cortical atrophy; MRI; Multiple sclerosis DOCUMENT TYPE: Article
martedì 21 giugno 2016
Il seminario informativo
'Sinergia tra Fondi strutturali e Horizon 2020 in Campania'
si terrà nell'
Aula Pessina dell'Università degli studi di Napoli Federico II,
Corso Umberto I, 40,
IL 24 GIUGNO ORE 10
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giovedì 16 giugno 2016
Lanzillo, B.a , Loreto, V.a , Calabrese, C.a , Estraneo, A.a , Moretta, P.a , Trojano, L.b
Does pain relief influence recovery of consciousness? A case report of a patient treated with ziconotide
(2016) European Journal of Physical and Rehabilitation Medicine, 52 (2), pp. 263-266. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84971408202&partnerID=40&md5=3e5b65d6c4d2d61ec2514a2b21c90914 AFFILIATIONS: a.Department of Neurorehabilitation, S. Maugeri IRCCS Foundation, Centro di Telese Terme Telese Terme, Via Bagni Vecchi 82037, Telese Terme (BN), Italy; b.Second University of Naples, Faculty of Psychology, Naples, Italy
ABSTRACT: For people with cervical spinal cord injury (SCI), access to computers can be difficult, thus several devices have been developed to facilitate their Disorders of consciousness (DOC) are difficult to classify. The degree of consciousness varies from coma to vegetative state or unresponsive wakefulness syndrome (UWS) and minimally conscious state. Correct diagnosis has important ethical and legal implications, and pain may be cause of misdiagnosis. We describe here a patient with traumatic brain injury, classified as UWS. His clinical picture was dominated by spasticity, and pain. He underwent intrathecal treatment of spasticity with baclofen. Improvement was not that expected. However, there was a dramatic improvement when ziconotide was added to relieve pain; the patient began to eat by mouth, talk, and his tracheal tube could be removed and he is currently classified as having severe disability. The suspension of ziconotide caused a clear re-worsening of clinical condition, reverted by his reintroduction. Pain is an important factor in patients with DOC. Anecdotal reports of improved consciousness with intrathecal baclofen therapy may be due to pain relief. Reduction of pain in DOC is important and drugs should not interfere with cognition, and must be effective and manageable. Ziconotide may be one of the possible candidate due to its synergistic antispastic action in combination with baclofen when an intratecal pump has been implanted. © 2015 EDIZIONI MINERVA MEDICA. AUTHOR KEYWORDS: Baclofen; Brain injuries; Consciousness Disorders; Pain; Ziconotide; Injections, spinal DOCUMENT TYPE: Article
mercoledì 15 giugno 2016
Boston Children's Hospital, Harvard Medical School Boston, Coordinator of Armenise-Harvard Summer Program for Italian Students (USA)
Intrinsic and extrinsic factors modulating the maturation of GABAergic interneurons
primo piano torre biologica ore 12
venerdì 10 giugno 2016
Femminella, G.D.a , De Lucia, C.a , Parisi, V.a , Silvestri, C.a , Petraglia, L.a , Formisano, R.a , Allocca, E.a , Ratto, E.a , Komici, K.a , Zincarelli, C.b , Rengo, F.b , Ferrara, N.b , Leosco, D.b
β-adrenergic receptor involvment in Alzheimer disease [Coinvolgimento del signaling β-adrenergico nella malattia di Alzheimer]
(2014) Giornale di Gerontologia, 62 (3), pp. 95-100. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84969857880&partnerID=40&md5=22a8afe856f495525916a63d2f42dc2c AFFILIATIONS: a. Dipartimento di Scienze Mediche Translazionali, Università di Napoli “Federico II”, Italy; b.Fondazione “Salvatore Maugeri”, IRCCS, Istituto Scientifico di Telese Terme (BN), Italy
ABSTRACT: Since 1907, when it was first described, Alzheimer’s disease (AD) has been one of the most studied diseases, in order to clarify its complex pathogenesis. Since AD will become increasingly widespread in the next decades, resulting in enormous health care costs. Since current treatments do not alter the course of the disease, acting temporarily on symptoms, it is essential to identify factors involved in the pathogenesis of disease. Among these, the β-adrenergic receptor (β-ARs) system might play a crucial role. The central noradrenergic system undergoes substantial changes in the course of AD and β-ARs have been implicated both in the formation of amyloid in brain and in amyloid-induced neurotoxicity. Furthermore, it has been shown that GRK2, a G protein-coupled receptor kinase which regulates receptor desensitization and downregolation, has been implicated in neuronal dysfunction caused by amyloid deposition. Finally, GRK2 levels in circulating lymphocytes, which correlate with cognitive impairment, may be used as a biomarker to monitor cognitive decline and response to therapy. © 2014, Pacini Editore S.p.A. All rights reserved. AUTHOR KEYWORDS: Alzheimer; Cognitive impairment; Dementia; β-adrenergic receptor; β-amyloid DOCUMENT TYPE: Review
Cell Death Dis. 2015 May 7;6:e1739. doi: 10.1038/cddis.2015.113.
Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice.
Bortolussi G1, Codarin E2, Antoniali G2, Vascotto C2, Vodret S1, Arena S3, Cesaratto L2, Scaloni A3, Tell G2, Muro AF1.
giovedì 9 giugno 2016
Prog Neuropsychopharmacol Biol Psychiatry. 2016 May 10;70:24-38. doi: 10.1016/j.pnpbp.2016.04.015. [Epub ahead of print]
Switching antipsychotics: Imaging the differential effect on the topography of postsynaptic density transcripts in antipsychotic-naïve vs. antipsychotic-exposed rats.
Copyright © 2016 Elsevier Inc. All rights reserved.
Amisulpride; Haloperidol; Homer; Treatment resistant schizophrenia
venerdì 3 giugno 2016
UNESCO Neuroscience Fellowships
Conference Date:1 October – 31 December 2016
Conference Venue:IBE-UNESCO headquarters in Geneva, Switzerland
Deadline:17th June 2016
Per maggiori dettagli vai al link: https://app.trialect.com/4125/display
Etichette: Borse di studio
giovedì 2 giugno 2016
Tomas-Roig, J.a b , Piscitelli, F.c , Gil, V.d , del Río, J.A.d , Moore, T.P.a b , Agbemenyah, H.e f , Salinas-Riester, G.g , Pommerenke, C.g , Lorenzen, S.h i , Beißbarth, T.h , Hoyer-Fender, S.j , Di Marzo, V.c , Havemann-Reinecke, U.a b
Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice
(2016) Behavioural Brain Research, 303, pp. 34-43.
a) Dept. of Psychiatry and Psychotherapy, University of Göttingen, Germany;
b) Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany;
c) Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy;
d) Institute for Bioengineering of Catalonia (IBEC), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Dept. of Cell Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain;
e) Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Göttingen, Germany;
f) University of Health and Allied Sciences, Ho, Ghana;
g) Dept. of Developmental Biochemistry, Göttingen, Germany;
h) Dept. of Medical Statistics, University Medical Center, Göttingen, Germany;
i) Dept. of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany;
j) Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, Developmental Biology, Göttingen, Germany
ABSTRACT: Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice. © 2016 Elsevier B.V.
Krashia, P.a , Ledonne, A.a , Nobili, A.a b , Cordella, A.a c , Errico, F.d e , Usiello, A.d f , D'Amelio, M.a b , Mercuri, N.B.a c , Guatteo, E.a , Carunchio, I.a c
Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons
(2016) Neuropharmacology, 103, pp. 69-78.
a) Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy;
b) Department of Medicine, Unit of Molecular Neurosciences, University Campus-Biomedico, Rome, Italy;
c) Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy;
d) Ceinge Biotecnologie Avanzate, Naples, Italy;
e) Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy;
f) Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples (SUN), Caserta, Italy
ABSTRACT: Dopamine neurons in the substantia nigra pars compacta regulate not only motor but also cognitive functions. NMDA receptors play a crucial role in modulating the activity of these cells. Considering that the amino-acid D-Aspartate has been recently shown to be an endogenous NMDA receptor agonist, the aim of the present study was to examine the effects of D-Aspartate on the functional properties of nigral dopamine neurons. We compared the electrophysiological actions of D-Aspartate in control and D-aspartate oxidase gene (Ddo-/-) knock-out mice that show a concomitant increase in brain D-Aspartate levels, improved synaptic plasticity and cognition. Finally, we analyzed the effects of L-Aspartate, a known dopamine neuron endogenous agonist in control and Ddo-/- mice. We show that D- and L-Aspartate excite dopamine neurons by activating NMDA, AMPA and metabotropic glutamate receptors. Ddo deletion did not alter the intrinsic properties or dopamine sensitivity of dopamine neurons. However, NMDA-induced currents were enhanced and membrane levels of the NMDA receptor GluN1 and GluN2A subunits were increased. Inhibition of excitatory amino-acid transporters caused a marked potentiation of D-Aspartate, but not L-Aspartate currents, in Ddo-/- neurons. This is the first study to show the actions of D-Aspartate on midbrain dopamine neurons, activating not only NMDA but also non-NMDA receptors. Our data suggest that dopamine neurons, under conditions of high D-Aspartate levels, build a protective uptake mechanism to compensate for increased NMDA receptor numbers and cell hyper-excitation, which could prevent the consequent hyper-dopaminergia in target zones that can lead to neuronal degeneration, motor and cognitive alterations. © 2015 Elsevier Ltd. All rights reserved.