Silvia Middei

Research Areas: Neurobiology


Monterotondo Scalo – Campus “A.Buzzati Traverso”
Research Gate Page
silvia.middei@cnr.it
People – CNR

My research investigates how brain networks work and how they are associated with both normal function, in particular memory and social behavior, and breakdown that lead to brain disorders.
My studies aim to assess brain activation, synaptic plasticity and the underlying neurobiological processes in transgenic mice for Alzheimer’s Disease (AD) and Autism Spectrum Disorders (ASDs) performing specific memory or social interaction tasks. These studies provide an understanding of how diseases affect neuronal networks underlying cognition.
Recent findings were the basis to testing a new AD-related drug (Scopa et al., 2019). In addition, I have investigated the compensatory activity of brain networks that sustains intact cognition at early stages of AD progression (Pignataro et al., 2019).
I am now running an international project to assess the neurobiological alterations underlying compulsive and avoidance behaviors in ASDs. The main research question in these studies is how exposition to social stimuli modulates the development of brain networks

Education

  • Feb 2001- Feb 2005 PhD in Neuroscience Tor Vergata University, Rome (Italy)                               
  • Nov 1993- Dec 1998     Master degree in Experimental Psychology   Sapienza University, Rome (Italy)

Positions:

  • Dec 2011-present  Researcher Tenure Track at National Research Council (Monterotondo) Institute of Biochemistry and Cell Biology
  • Dec 2007-Nov 2011       Research Scientist at European Brain Research Centre (Rome)
    Santa Lucia Foundation
  • Nov 2005-Nov 2007       Post Doc Research Fellow at Trinity College (Dublin, Ireland)                Institute for Neuroscience
  • Nov 2001- Feb 2005      PhD in Neuroscience Tor Vergata University, Rome (Italy)- Santa Lucia Foundation and Sigma Tau

Honours/Awards:

  1. IRCSET Embark Initiative, 2005
  2. Italian Society for Neuroscience, 2005
  3. FENS/Hertie Foundation, 2004
  4. European Science Foundation, 2004
  5. European Science Foundation, 2002

  • Pignataro A, Meli G, Pagano R, Fontebasso V, Battistella R, Conforto G, Ammassari-Teule M, Middei S. Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer’s Disease Mice. Biol Psychiatry. 2019 Aug 1;86(3):185-195
  • Rizzello E, Middei S, Marchetti C Synaptic Correlates of Anterograde Amnesia and Intact Retrograde Memory in a Mouse Model of Alzheimer’s Disease. Curr Alzheimer Res. 2020 Feb 24:10.2174/1567205017666200224122113
  • Pignataro A, Middei S. Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis. Neural Plast. 2017;2017:5281829
  • Scopa C, Marrocco F, Latina V, Ruggeri F, Corvaglia V, La Regina F, Ammassari-Teule M, Middei S, Amadoro G, Meli G, Scardigli R, Cattaneo A.Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ. 2020 Mar;27(3):934-948
  • Scopa C, Marrocco F, Latina V, Ruggeri F, Corvaglia V, La Regina F, Ammassari-Teule M, Middei S, Amadoro G, Meli G, Scardigli R, Cattaneo A.Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ. 2020 Mar;27(3):934-948

Publications as corresponding author:    

  1. Rizzello E, Middei S,Marchetti C Synaptic Correlates of Anterograde Amnesia and Intact Retrograde Memory in a Mouse Model of Alzheimer’s Disease. Curr Alzheimer Res. 2020 Feb 24:10.2174/1567205017666200224122113
  2. Pignataro A, Meli G, Pagano R, Fontebasso V, Battistella R, Conforto G, Ammassari-Teule M, Middei S. Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer’s Disease Mice. Biol Psychiatry. 2019 Aug 1;86(3):185-195
  3. Pignataro A, Middei S. Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis. Neural Plast. 2017;2017:5281829.
  4. Pignataro A, Borreca A, Ammassari-Teule M, Middei S. CREB Regulates Experience-Dependent Spine Formation and Enlargement in Mouse Barrel Cortex. Neural Plast. 2015;2015:651469.
  5. Middei S, Houeland G, Cavallucci V, Ammassari-Teule M, D’Amelio M, Marie H. CREB is necessary for synaptic maintenance and learning-induced changes of the AMPA receptor GluA1 subunit. Hippocampus. 2013 Jun;23(6):488-99.
  6. Middei S, Spalloni A, Longone P, Pittenger C, O’Mara SM, Marie H, Ammassari-Teule M. CREB selectively controls learning-induced structural remodeling of neurons. Learn Mem. 2012 Jul 18;19(8):330-6.
  7. Middei S, Roberto A, Berretta N, Panico MB, Lista S, Bernardi G, Mercuri NB, Ammassari-Teule M, Nisticò R. Learning discloses abnormal structural and functional plasticity at hippocampal synapses in the APP23 mouse model of Alzheimer’s disease. Learn Mem. 2010 Apr 19;17(5):236-40
  8. Middei S, Restivo L, Caprioli A, Aceti M, Ammassari-Teule M. Region-specific changes in the microanatomy of single dendritic spines over time might account for selective memory alterations in ageing hAPPsweTg2576 mice, a mouse model for Alzheimer disease. Neurobiol Learn Mem. 2008 Sep;90(2):467-71.
  9. Middei S, Vetere G, Sgobio C, Ammassari-Teule M. Landmark-based but not vestibular-based orientation elicits mossy fiber synaptogenesis in the mouse hippocampus. Neurobiol Learn Mem. 2007 Feb;87(2):174-80.
  10. Middei S, Daniele S, Caprioli A, Ghirardi O, Ammassari-Teule M. Progressive cognitive decline in a transgenic mouse model of Alzheimer’s disease overexpressing mutant hAPPswe. Genes Brain Behav. 2006 Apr;5(3):249-56.

Other publications:

  1. Scopa C, Marrocco F, Latina V, Ruggeri F, Corvaglia V, La Regina F, Ammassari-Teule M, Middei S, Amadoro G, Meli G, Scardigli R, Cattaneo A.Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ. 2020 Mar;27(3):934-948.
  2. Nicolis di Robilant V, Scardigli R, Strimpakos G, Tirone F, Middei S, Scopa C, De Bardi M, Bttistini L, Saraulli D, Farioli Vecchioli S. Running-activated  neural stem cells enhance subventricular neurogenesis and improve  olfactory behaviour in p21 knockout mice. Mol Neurobiol. 2019 Nov;56(11):7534-7556
  3. Borreca A, Latina V, Corsetti V, Middei S, Piccinin S, Della Valle F, Bussani R, Ammassari-Teule M, Nisticò R, Calissano P, Amadoro G. AD-Related N-Terminal Truncated Tau Is Sufficient to Recapitulate In Vivo the Early Perturbations of Human Neuropathology: Implications for Immunotherapy. Mol Neurobiol. 2018 Oct;55(10):8124-8153.
  4. Pignataro A, Pagano R, Guarneri G, Middei S, Ammassari-Teule M. Extracellular matrix controls neuronal features that mediate the persistence of fear. Brain Struct Funct. 2017 Dec;222(9):3889-3898.
  5. Criscuolo C, Fontebasso V, Middei S, Stazi M, Ammassari-Teule M, Yan S, Origlia N. Entorhinal Cortex dysfunction can be rescued by inhibition of microglial RAGE in an Alzheimer’s disease mouse model. Sci Rep 2017 Feb 13; (7): 42370
  6. Ehrmann I, Gazzara MR, Pagliarini V, Dalgliesh C, Kheirollahi-Chadegani M, Xu Y, Cesari E, Danilenko M, Maclennan M, Lowdon K, Vogel T, Keskivali-Bond P, Wells S, Cater H, Fort P, Santibanez-Koref M, Middei S, Sette C, Clowry GJ, Barash Y, Cunningham MO, Elliott DJ. A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. Cell Rep. 2016 Dec 20;17(12):3269-3280.
  7. Vannini E, Olimpico F, Middei S, Ammassari-Teule M, de Graaf EL, McDonnell L, Schmidt G, Fabbri A, Fiorentini C, Baroncelli L, Costa M, Caleo M. Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function. Neuro Oncol. 2016 Dec;18(12):1634-1643.
  8. Antonelli R, De Filippo R, Middei S, Stancheva S, Pastore B, Ammassari-Teule M, Barberis A, Cherubini E, Zacchi P. Pin1 Modulates the Synaptic Content of NMDA Receptors via Prolyl-Isomerization of PSD-95. J Neurosci. 2016 May 18;36(20):5437-47.
  9. Vannini E, Restani L, Pietrasanta M, Panarese A, Mazzoni A, Rossetto O, Middei S, Micera S, Caleo M. Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks. Brain Struct Funct. 2016 Jul;221(6):2919-36.
  10. Oddi D, Subashi E, Middei S, Bellocchio L, Lemaire-Mayo V, Guzmán M, Crusio WE, D’Amato FR, Pietropaolo S. Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome. Neuropsychopharmacology. 2015 Mar 13;40(5):1113-22.
  11. Middei S, Ammassari-Teule M, Marie H. Synaptic plasticity under learning challenge. Neurobiol Learn Mem. 2014 Nov;115:108-15.
  12. Errico F, Nisticò R, Di Giorgio A, Squillace M, Vitucci D, Galbusera A, Piccinin S, Mango D, Fazio L, Middei S, Trizio S, Mercuri NB, Teule MA, Centonze D, Gozzi A, Blasi G, Bertolino A, Usiello A. Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals. Transl Psychiatry. 2014 Jul 29;4:e417.
  13. Pignataro A, Middei S, Borreca A, Ammassari-Teule M. Indistinguishable pattern of amygdala and hippocampus rewiring following tone or contextual fear conditioning in C57BL/6 mice. Front Behav Neurosci. 2013 Oct 29;7:156.
  14. Pignatelli M, Vollmayr B, Richter SH, Middei S, Matrisciano F, Molinaro G, Nasca C, Battaglia G, Ammassari-Teule M, Feligioni M, Nisticò R, Nicoletti F, Gass P. Enhanced mGlu5-receptor dependent long-term depression at the Schaffer collateral-CA1 synapse of congenitally learned helpless rats. Neuropharmacology. 2013 Mar;66:339-47.
  15. D’Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A, Diamantini A, De Zio D, Carrara P, Battistini L, Moreno S, Bacci A, Ammassari-Teule M, Marie H, Cecconi F. Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease. Nat Neurosci. 2011 Jan;14(1):69-76.
  16. Marchetti C, Tafi E, Middei S, Rubinacci MA, Restivo L, Ammassari-Teule M, Marie H. Synaptic adaptations of CA1 pyramidal neurons induced by a highly effective combinational antidepressant therapy. Biol Psychiatry. 2010 Jan 15;67(2):146-54.
  17.  Vergni D, Castiglione F, Briani M, Middei S, Alberdi E, Reymann KG, Natalini R, Volonté C, Matute C, Cavaliere F. A model of ischemia-induced neuroblast activation in the adult subventricular zone. PLoS One. 2009;4(4):e5278.
  18. Giampà C, Middei S, Patassini S, Borreca A, Marullo F, Laurenti D, Bernardi G, Ammassari-Teule M, Fusco FR. Phosphodiesterase type IV inhibition prevents sequestration of CREB binding protein, protects striatal parvalbumin interneurons and rescues motor deficits in the R6/2 mouse model of Huntington’s disease. Eur J Neurosci. 2009 Mar;29(5):902-10.
  19. Bellenchi GC, Gurniak CB, Perlas E, Middei S, Ammassari-Teule M, Witke W. N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex. Genes Dev. 2007 Sep 15;21(18):2347-57.
  20. Ognibene E, Middei S, Daniele S, Adriani W, Ghirardi O, Caprioli A, Laviola G. Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer’s disease. Behav Brain Res. 2005 Jan 30;156(2):225-32.
  21. Middei S, Restivo L, Sgobio C, Passino E, Ammassari-Teule M. Reversible inactivation of hippocampus and dorsolateral striatum in C57BL/6 and DBA/2 inbred mice failed to show interaction between memory systems in these genotypes. Behav Brain Res. 2004 Oct 5;154(2):527-34.
  22. Middei S, Geracitano R, Caprioli A, Mercuri N, Ammassari-Teule M. Preserved fronto-striatal plasticity and enhanced procedural learning in a transgenic mouse model of Alzheimer’s disease overexpressing mutant hAPPswe. Learn Mem. 2004 Jul-Aug;11(4):447-52.
  23. Restivo L, Middei S, Mingfu L, Reggio R, Passino E, Formisano R, Ammassari-Teule M. Potentiation of ischemia-related behavioral alterations by electro-acupuncture in gerbils. Funct Neurol. 2004 Jan-Mar;19(1):19-23
  24. Ammassari-Teule M, Middei S, Passino E, Restivo L. Enhanced procedural learning following beta-amyloid protein (1-42) infusion in the rat. Neuroreport. 2002 Sep 16;13(13):1679-82.
  25. Aversano M, Ciamei A, Cestari V, Passino E, Middei S, Castellano C. Effects of MK-801 and ethanol combinations on memory consolidation in CD1 mice: involvement of GABAergic mechanisms. Neurobiol Learn Mem. 2002 May;77(3):327-37.
  26. Passino E, Middei S, Restivo L, Bertaina-Anglade V, Ammassari-Teule M. Genetic approach to variability of memory systems: analysis of place vs. responselearning and fos-related expression in hippocampal and striatal areas of C57BL/6 and DBA/2 mice. Hippocampus. 2002;12(1):63-75.
  27. Restivo L, Passino E, Middei S, Ammassari-Teule M. The strain-specific involvement of nucleus accumbens in latent inhibition might depend on differences in processing configural- and cue-based information between C57BL/6 and DBA mice. Brain Res Bull. 2002 Jan 1;57(1):35-9

CNR Short term mobility grant, Year 2018. Project title: Modulation of Oxytocin system in a mouse model of Fragile X Syndrome. Role in the project: PI (Collaborator: Susanna Pietropaolo, Bordeaux University, France)

CNR Research grant on Health ageing, Years 2013-2016. Project title: Disease mechanisms of working memory load capacity in ageing and Alzheimer’s Disease. AGESPAM IGB-CNR. Role in the project: Collaborator (Coordinator: Martine Ammassari-Teule, Santa Lucia Foundation, Rome, Italy)

Alzheimer Association Grant, Years 2012-2014. Project title: Learning from epilepsy to understand Alzheimer’s Disease. NIRG-12-237009. Role in the project: co-PI (PI, Cristina Marchetti, European Brain Research Institute, Rome, Italy)

Alzheimer Association Grant, Years 2011-2013. Project title: Preventing and monitoring onset of synaptic degeneration in early Alzheimer’s Disease. NIRG-11-204588. Role in the project: Collaborator (PI: Marcello D’Amelio, Santa Lucia Foundation, Rome, Italy)

FILAS, Starting Grant 2011. Project title: Sviluppo delle ricerche sul cervello: Aspetti molecolari e comportamentali delle malattie del Sistema Nervoso. DSB.AD004,089. Role in the project: Unit PI (Coordinator Delio Mercanti).