Expertise and current research performed: The proposed research work will be conducted in the laboratory of Dr. Marina Bentivoglio in the Department of Morphological and Biomedical Sciences (http://www.dsmb.univr.it/main?ent=persona&id=1069&lang=en), and in the Center of Experimental Nuclear Magnetic Resonance Imaging (MRI) of CR3 UNIVR. Dr. Bentivoglio’s laboratory is engaged since several years in research on experimental epilepsy, with emphasis on the study of neural circuit rearrangement involved in epileptogenesis and maintenance of chronic seizures, their molecular regulation and neuroimaging correlates, the neuroinflammatory response elicited by seizures. Data on the epileptic brain are also compared in the laboratory with those obtained in other paradigms of neuroinflammation and neurodegeneration. Ongoing projects of the laboratory include: (1) Analysis of cortical and diencephalic involvement in pilocarpine-induced epilepsy, to unravel structures and mechanisms of secondary generalization of seizures. (2) Analysis of glial (astrocytic and microglial) contribution to epileptogenesis. (3) Animal models of pharmacoresistant epilepsy due to delayed initiation of anti-epileptic therapy, and (4) of resistance to epilepsy. (5) study of the expression (at the mRNA and protein levels) of glial and neuronal connexins (which build-up gap-junctional communication or electrical coupling) in experimental limbic epilepsy in rats. (6) Cell cultures of different glial populations have been set up for calcium imaging studies after challenges with convulsant agents.

Facilities/Equipment: The Partner facilities include a molecular biology lab, cell culture facilities, a behavioural lab equipped with telemetric monitoring system and Ethovision system for behavioural studies, histology lab with image analysis systems, confocal and electron microscopy (scanning and transmission EM), access to laser microdissection equipment. The fully equipped MRI Center allows functional and structural MRI, with physiological monitoring, in small animals – rats and mice-, as well as photon spectroscopy.

Personnel involved in the project

Principal investigator: Marina Bentivoglio (F). Full Professor of Histology, MD and specialist in Clinical Neurology, with training in human and experimental neuropathology, has a long experience in basic and applied research in neuroscience. Member of the PhD Curriculum in Neuroscience of CR3 UNIVR, has longstanding experience as counselor in scientific organizations and societies (e.g. the Society for Neuroscience and the International Brain Research Organization, IBRO; she is President Elect of the Italian Society for Neuroscience), and editorial experience. Paolo Fabene (M). Assistant Professor of Anatomy, PhD, has specific expertise in rodent models of epilepsy, behavioural testing including telemetric recording, and neuroimaging studies. Andrea Sbarbati (M). MD, Full Professor of Anatomy, has specific expertise in imaging approaches and in electron microscopy. Giuseppe Bertini (M). MD, Assistant Professor of Histology, has special expertise in neural plasticity phenomena and behavioural studies. Pasquina Marzola (F). PhD, physicist, Assistant Professor of Medical Physics, has longstanding experience in MRI approaches and techniques. Anna Andrioli (F). Degree in Psychology, graduate student in Neuroscience (3^rd year), is expert in animal models of limbic epilepsy and brain damage. Anna Andrioli will be hired as a post-doc for the project (half of her stipend would be EU-funded). Marta Bonaconsa (F). Degree in Biological Sciences, graduate student in Neuroscience (2^nd year). Training in molecular biology approaches.

Two additional graduate students (non-EU funded) would be dedicated to the project.

Recent relevant publications/patents

1.        Fabene P.F., Weiczner R., Marzola P., Nicolato E., Calderan L., Andrioli A., Farkas E., Süle Z., Mihaly A., Sbarbati A. (2005) Structural and functional MRI following 4-aminopyridine-induced seizures: a direct histological and ultrastructural correlation. Neurobiol Dis. (in press).

2.        Fabene P.F., Andrioli A., Priel M.R., Cavalheiro E.A., Bentivoglio M. (2004) Fos induction and persistence, neurodegeneration, and interneuron activation in the hippocampus of epilepsy-resistant versus epilepsy-prone rats after pilocarpine-induced seizures. Hippocampus 14: 895-907.

3.        Fabene P.F., Marzola P., Sbarbati A., Bentivoglio M. (2003) Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain: diffusion-weighted and T2-weighted images, regional blood volume maps, and direct correlation with tissue and cell damage. NeuroImage 18: 375-389.

4.        Kong G.-Y., Kristensson K., Bentivoglio M. (2002) Reaction of mouse brain oligodendrocytes and their precursors, astrocytes and microglia to proinflammatory mediators circulating in the cerebrospinal fluid. Glia, 37: 191-205.

5.        Fabene P.F., Correia L., Carvalho R.A., Cavalheiro E.A., Bentivoglio M. (2001) The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes, Neuroscience 104: 979-1002.