Elvira De Leonibus
Head of Behavioral Core, TIGEM
PI Neuropsychopharmacology Lab, Institute of Genetics and Biophysics, National Research Council, Italy
Assistant professor of Psychobiology, MIUR, Italy
Lecturer in Neuropsychopharmacology, University of Rome “La Sapienza”, Italy
TIGEM’s Behavioral Core has three principal objectives. It aims to identify abnormal behaviors in animal models that may be associated with gene deletions or mutations pertaining to our human genetic diseases of interest. Upon finding such information, the Core tests whether and to which extent novel pharmacological or gene therapy techniques can be used to rescue these behavioral alterations. Last but not least, the Core organizes novel behavioural tasks and procedures to study rodent behavior in mice, rats, hamsters.
The Core combines basic knowledge of the biological processes underlying animal behavior with systematic use of the whole battery of behavioral tests available for rodents to date.
In support of its research, the Behavioral Core is equipped with more than 30 different behavioral task tools (i.e. activity cage, elevated plus-maze, hot-plate, water maze, cross-maze, grip-strength meter, passive and active avoidance apparatus) for mice, rats and hamsters, which allow it to test basic sensory-motor functions, learning and memory processes and emotional behaviors. The Core personnel helps and assists researchers in the planning, execution, data analysis, data interpretation, results dissemination, and application for grant funding for all behavioral and behavioral-pharmacogenetic experiments. Since its establishment in September 2007, the Core behavioral group has established eleven internal collaborations that have led to an accumulation of experience specific to the behavioral phenotyping of many different genetic animal models of human genetic diseases.
The Behavioral Core has worked to identify behavioral alterations in animal models of lysosomal storage disorders, in particular in those of mucopolysaccharidoses. Mucopolysaccharidoses are a group of monogenic, rare, incurable disorders affecting children. Some lead to progressive bone and articular defects (i.e. MPSVI), some cause neurodegeneration (i.e. MPS-III and MPS-II) and others generate both types of phenotypes (i.e. MSD). In the past years we have identified some specific behavioral alterations in each of these animals models, which we consider helpful parameters to test the efficacy and side effects of novel therapeutic strategies in vivo.
Finally, we are combining our expertise of lysosomal storage disorders with that of neuropsychopharmacology of learning and memory to identify early neurochemical dysfunction, which leads to the neurobehavioral phenotype in MPS animal’ models. These studies will add important information and help to explain the neurochemical changes that occur in MPS and affect the central nervous system. This may give new insights into the diseases mechanisms that originate as lysosomal storage disorders and lead to neurodegeneration.
Saccone P, Cotugno G, Russo F, Mastrogiacomo R, Tessitore A, Auricchio A, De Leonibus E (2014). Sensory-motor behavioural characterization of an animal model of Maroteaux-Lamy syndrome (or Mucopolysaccharidosis VI). Scientific Reports. 4:3644. doi:10.1038/srep03644.
Sorrentino NC, D’Orsi L, Nusco E, Sambri I, Spampanato C, Polishchuk E, Saccone P, De Leonibus E, Ballabio A, Fraldi A (2013). A highly secreted sulfamidase engineered to cross the blood-brain barrier corrects the CNS pathology of mice with mucopolysaccharidosis type IIIA. EMBO Molecular Medicine. 5(5):675-90. doi:10.1002/emmm.201202083.
Managò F, Lopez S, Oliverio A, Amalric M, Mele A, De Leonibus E (2012). Interaction between the mGlu receptors 5 antagonist, MPEP, and amphetamine on memory and motor functions in mice. Psychopharmacology. doi: 10.1007/s00213-012-2925-4.
Sanino S*, Russo F*, Torromino G, Pendolino V, Calabresi P, De Leonibus E (2012). Role of the hippocampus in object memory load. Learning & Memory. 19: 211-18. doi: 10.1101/lm.025213.111.
Spampanato C*, De Leonibus E*, Dama P, Gargiulo A, Fraldi A, Sorrentino CN, Russo F, Nusco E, Auricchio A, Surace EM, Ballabio A (2010). Efficacy of a combined intracerebral and systemic gene delivery approach for the treatment of a severe lysosomal storage disorder. Human Molecular Genetics. 19(5):860-9. doi: 10.1038/mt.2010.299.
The Neuropsychopharmacology Group, also headed by Elvira De Leonibus, applies the neurobiology of learning and memory to studies under normal and pathological conditions. Memory is a fundamental brain function for animal survival. In our lab we strive to answer questions related to the neurobiology of memory and focus on the roles of dopamine, glutamate and their interactions in different brain regions.
Recently we have attempted to understand how the brain processes increasing information loads. This is a question of fundamental importance, especially in the information era in which we are living. It has been estimated, that as a result of the information revolution, we are receiving (via television, internet, etc) five times as much information as we did in 1986. This fact is related to memory capacity (MC), which in psychology refers to the limited capacity of working memory (WM), and more in general to the limited capacity of our mental resources. Although, memory capacity is a hot topic in neuropsychology, the neurobiology of normal and pathological MC is almost completely unexplored.
We have recently developed a novel behavioral procedure to study MC in rodents (Sannino et al 2012), the DOT-IOT. Using the DOT-IOT we have demonstrated that mice, as well as humans, also have a limited MC. By combining behavioral, genetic, pharmacological and molecular approaches, we are finding new information on the molecular pathways supporting memory load capacity and disease mechanisms that cause memory capacity dysfunctions in neurodegenerative and psychiatric disorders, such as Alzheimer’ disease, Parkinson’s disease, senescence, and schizophrenia.