• memory
• Enriched Environment
• consolidation
• cognitive stimulation
• aging
• Mild Cognitive Impairment

Brain aging is a complex physiological process which includes an age related cognitive decline, particularly evident for long term declarative memory, working memory, attention and processing speed. There is a large literature of epidemiological studies in humans which suggests that lifestyle factors, such as physical activity, cognitive activity and social interactions, factors which are the main components of an “enriched environment”, can be protective against the development of pathological cognitive decline in elders and reduce the incidence of dementia. In parallel, studies in animals have shown that exposure to an Enriched Environment markedly improves memory performance in aged animals. This would suggest that interventions based on the “enriched environment” paradigm might benefit the cognitive status of elders. However, the literature reports no study investigating the effects of an intervention based on the combination of cognitive and physical training in aged humans already showing signs of cognitive impairment. In Pisa such a study is currently active and is the project “Train the Brain”, employing a combination of physical exercise, cognitive training and stimulation in a social setting to test whether such a non-pharmacological treatment is effective in decreasing the rate of cognitive impairment or even in obtaining a cognitive enhancement in subject with Mild Cognitive Impairment (MCI), considered subjects at risk for developing dementia.
During my PhD, within the project “Train the Brain”, I have analysed the effects of 7 months of a physical and cognitive training program in a social setting in subject with MCI using a neuropsychological battery to assess the effects of the intervention at the end of the 7 months and in subsequent follow-up tests.
In parallel I have addressed the possible mechanisms of action of an Enriched Environment on cognitive aging exploiting animal models.
The formation of long term declarative memories is a process mediated by the hippocampus and other medial temporal lobe structures and relies upon plasticity mechanisms in these structures, which allows a first, local, consolidation of the memory trace; however, it has been recently shown that for context-rich declarative memories, such as episodic memory, the successful recall of memory traces at some temporal
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distance from their formation requires the additional contribution of neocortical structures, which are progressively recruited for memory storage and recall in a process called memory system consolidation. A crucial mechanism underlying memory system consolidation consists in the functional and structural reorganisation of the pattern of cortical region activation prompted by the reactivation of hippocampal-cortical pathways and the strengthening of cortico-cortical connections, and with the fundamental involvement of cortical plasticity processes. While age related changes in hippocampal plasticity which might underlie age related changes in long-term declarative memory formation have been deeply investigated, no attempt has yet been done to investigate whether system consolidation is impaired by brain aging. Surprisingly, system consolidation has not even been considered as a possible target of the action of enriched environmental conditions in enhancing brain plasticity and improving memory performance in adult or aged animals.
I have first tested whether Enriched Environment (EE) could affect the system consolidation process in adult mice: in particular, I investigated whether EE could accelerate the time course of the activation of neocortical areas, possibly through a strengthening of the hippocampal-cortical and the cortico-cortical connections. To do so, I characterized the time course of hippocampal and cortical activation following spatial learning in a brain-wide manner following recalls delayed up to 50 days, using the expression of c-Fos protein as an indicator of neuronal activity in the different brain regions examined.
In a second experiment I studied whether EE could affect memory system consolidation in aged mice. To pinpoint the post-learning mechanisms underlying the hippocampal-cortical dialogue during the course of system-level memory consolidation, I trained aged mice, either left in standard cages or put for 40 days in EE, in the social transmission of food preference test (STFP), which involves an ethologically based form of associative olfactory memory. Mice have been tested for memory retrieval either 1 day (recent memory) or 30 days (remote memory) later and system consolidation investigated assessing the pattern of brain area activation and the state of histone acetylation in prefrontal cortical areas.