AMIRA SAIDI

PhD Graduate

PhD program:: XXXIII



Thesis title: Microglia-complement implication and structural-functional synaptic characterization in the hippocampus of early Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS) in which the immune system plays a central role to drive pathology. In addition to motor and sensory symptoms, memory impairment is reported in MS patients in early stage of the disease and in rodent models prior to the disease onset. The synaptic pruning is a physiological developmental mechanism, crucial for brain connectivity in which the complement components C1q-C3 and the phagocytic receptors expressed by microglia, C3R and Trem2, have been implicated. A reactivation of similar mechanism may be one of the central causes of the synapses loss in neurodegenerative disorders including MS and might explain the early synaptic changes occurring within the hippocampus. In this thesis, we have analyzed the demyelination process, the classical complement components activation and the synapse-microglia interaction in the hippocampus of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have focused on the earliest stage (i.e. after induction), when motor symptoms are still not observed. Furthermore we have investigated the role of microglia phagocytic receptors Trem2 and C3R and the classical complement component C3 in the disease progression. Following immunohistochemical analysis, we have found no demyelination or microglial activation, as well as unaltered complement components expression levels. In addition, we have found no changes in the synaptic density within the hippocampus of the asymptomatic EAE mice, compared to their controls. Notably, we have found an increased VGAT expression in the CA1 region of the hippocampus at day 8 post-immunization which reflects a subtle alteration of inhibitory neurotransmission but whose significance is still unclear. Moreover, electrophysiological examination of the hippocampal synaptic transmission and plasticity did not establish any changes on synaptic function at the earliest stage after induction. However, genetic deletion of complement protein C3 and its receptor subunit CD11b reduces motor symptom severity in EAE mouse but has no effect on the disease onset. We then sought to determine the role of Trem2 receptor on clinical motor score severity. Unexpectedly, inducing EAE in Trem2 knockout mice is associated with a reduction in clinical score and in the demyelination progression. To sum up, we believe that hippocampus synaptic degeneration occurs late in the disease, when motor symptoms are well established. Overall, we have confirmed the role of classical complement components C3 and C3R in the EAE progression and disease manifestation, and we have identified Trem2 receptor as a potential anti-inflammatory target for a disease modifying therapy.

Research products

11573/1620725 - 2021 - Targeting microglia‐synapse interactions in alzheimer’s disease
Piccioni, G.; Mango, D.; Saidi, A.; Corbo, M.; Nistico, R. - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 1-17 - issn: 1661-6596 - wos: WOS:000628273600001 (27) - scopus: 2-s2.0-85101570062 (36)

11573/1277455 - 2019 - The positive allosteric modulator at mGlu2 receptors, LY487379, reverses the effects of chronic stress-induced behavioral maladaptation and synaptic dysfunction in the adulthood
Mango, Dalila; Caruso, Alessandra; Saidi, Amira; Nisticò, Robert; Scaccianoce, Sergio - 01a Articolo in rivista
paper: SYNAPSE (John Wiley & Sons Incorporated:Customer Service, 111 River Street:Hoboken, NJ 07030:(800)225-5945, (201)748-6000, EMAIL: societyinfo@wiley.com, INTERNET: http://www.wiley.com, Fax: (212)748-6551) pp. - - issn: 0887-4476 - wos: WOS:000474589500001 (4) - scopus: 2-s2.0-85066885318 (5)

11573/1336057 - 2019 - Targeting Synaptic Plasticity in Experimental Models of Alzheimer's Disease
Mango, Dalila; Saidi, Amira; Cisale, Giusy Ylenia; Feligioni, Marco; Corbo, Massimo; Nisticò, Robert - 01g Articolo di rassegna (Review)
paper: FRONTIERS IN PHARMACOLOGY (Lausanne: Frontiers Media S.A., 2010-) pp. 778- - issn: 1663-9812 - wos: WOS:000475895400001 (32) - scopus: 2-s2.0-85076180103 (34)

11573/1114130 - 2018 - Stress as risk factor for Alzheimer's disease
Caruso, Alessandra; Nicoletti, Ferdinando; Mango, Dalila; Saidi, Amira; Orlando, Rosamaria; Scaccianoce, Sergio - 01a Articolo in rivista
paper: PHARMACOLOGICAL RESEARCH (Attuale:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 24-28 OVAL RD, LONDON, ENGLAND, NW1 7DX Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. 130-134 - issn: 1043-6618 - wos: WOS:000436914000014 (69) - scopus: 2-s2.0-85046104438 (74)

11573/1179555 - 2018 - Sex differences in functional and molecular neuroimaging biomarkers of Alzheimer's disease in cognitively normal older adults with subjective memory complaints
Cavedo, Enrica; Chiesa, Patrizia A.; Houot, Marion; Ferretti, Maria Teresa; Grothe, Michel J.; Teipel, Stefan J.; Lista, Simone; Habert, Marie-Odile; Potier, Marie-Claude; Dubois, Bruno; Hampel, Harald; Bakardjian, Hovagim; Benali, Habib; Bertin, Hugo; Bonheur, Joel; Boukadida, Laurie; Boukerrou, Nadia; Cavedo, Enrica; Chiesa, Patrizia; Colliot, Olivier; Dubois, Bruno; Dubois, Marion; Epelbaum, Stéphane; Gagliardi, Geoffroy; Genthon, Remy; Habert, Marie-Odile; Hampel, Harald; Houot, Marion; Kas, Aurélie; Lamari, Foudil; Levy, Marcel; Lista, Simone; Metzinger, Christiane; Mochel, Fanny; Nyasse, Francis; Poisson, Catherine; Potier, Marie-Claude; Revillon, Marie; Santos, Antonio; Andrade, Katia Santos; Sole, Marine; Surtee, Mohmed; De Schotten, Michel Thiebaud; Vergallo, Andrea; Younsi, Nadjia; Aguilar, Lisi Flores; Babiloni, Claudio; Baldacci, Filippo; Benda, Norbert; Black, Keith L.; Bokde, Arun L. W.; Bonuccelli, Ubaldo; Broich, Karl; Bun, René S.; Cacciola, Francesco; Castrillo, Juan; Cavedo, Enrica; Ceravolo, Roberto; Chiesa, Patrizia A.; Colliot, Olivier; Coman, Cristina-Maria; Corvol, Jean-Christophe; Cuello, Augusto Claudio; Cummings, Jeffrey L.; Depypere, Herman; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Escott-Price, Valentina; Federoff, Howard; Ferretti, Maria Teresa; Fiandaca, Massimo; Frank, Richard A.; Garaci, Francesco; Genthon, Remy; George, Nathalie; Giorgi, Filippo S.; Graziani, Manuela; Haberkamp, Marion; Habert, Marie-Odile; Hampel, Harald; Herholz, Karl; Karran, Eric; Kim, Seung H.; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lista, Simone; Lorenceau, Jean; Mapstone, Mark; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; O'bryant, Sid E.; Perry, George; Ritchie, Craig; Rojkova, Katrine; Rossi, Simone; Saidi, Amira; Santarnecchi, Emiliano; Schneider, Lon S.; Sporns, Olaf; Toschi, Nicola; Verdooner, Steven R.; Vergallo, Andrea; Villain, Nicolas; Welikovitch, Lindsay A.; Woodcock, Janet; Younesi, Erfan - 01a Articolo in rivista
paper: ALZHEIMER'S & DEMENTIA (New York : Elsevier, c2005-) pp. 1204-1215 - issn: 1552-5260 - wos: WOS:000444008800011 (72) - scopus: 2-s2.0-85052864283 (74)

11573/1120332 - 2018 - Precision medicine and drug development in Alzheimer's disease: the importance of sexual dimorphism and patient stratification
Hampel, Harald; Vergallo, Andrea; Giorgi, Filippo Sean; Kim, Seung Hyun; Depypere, Herman; Graziani, Manuela; Saidi, Amira; Nisticò, Robert; Lista, Simone - 01a Articolo in rivista
paper: FRONTIERS IN NEUROENDOCRINOLOGY (Orlando, Fla.: Academic Press.) pp. - - issn: 0091-3022 - wos: WOS:000445443600004 (38) - scopus: 2-s2.0-85048395172 (44)

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