Titolo: The sheep as a translational model to study structural, biochemical and behavioral changes associated to brain aging

Bando: PRIN

Durata: 24 mesi

Coordinatore: PROF. BRUNO COZZI

Budget BCA: € 62.424,00

Responsabile scientifico: prof.ssa Antonella Peruffo

Research Team: Cozzi Bruno, Peruffo Antonella

Abstract: The population of the Western world is aging, thanks to the improved health and social systems and consequent reduced mortality. In ths sense, a better understanding of the biology and physiology of aging is essential. Sociological and psychological studies on the elderly provide fundamental insights into how the brain and the mind age, while clinical studies on the impairment of cognitive processes add other elements to complete the picture. The use of laboratory rodents is also important for the progress of knowledge, as experimental data allow testing of different hypothesis and conditions. The currently prevailing rodent model in neuroscience still remains the gold standard in translational research. However remarkable differences do exist in complex biological processes between rodents and large-brained mammals, thus reducing the translational value of the formers (see Manger et al., 2008; La Rosa & Bonfanti, 2018; Piumatti et al., 2018; Cozzi et al., 2020; La Rosa et al., 2020). In the present Grant application, we propose to use the sheep as translational model for the study of aging. This quite common ruminant mammal is usually raised for wool, milk, and meat production. The brains can be collected during the slaughtering process of animals sacrificed for commercial reasons in many abattoirs. A preliminary search showed that sheep of different age classes can be easily found in local farms and can be used for behavioral tests of motor and cognitive abilities. Freely moving sheep can also be used in non-invasive investigations aimed at the study of the cerebral circulation and oxygenation. We plan to use a multidisciplinary approach to the study of the aging ovine brain. Neurochemical and biochemical studies will yield data on the changes in the laminar organization of the cortical column and the biochemical expression of markers of cognitive decline in animals of different age classes. Behavioral studies will clarify whether age and potential changes in oxygenation of the brain are associated to alterations in motor and cognitive performances. Taken together, the results of the planned experiments may contribute to a progress in the field, and help validate the use of the sheep as a trustable translational model in current ageing research.