Stefano Morara

Nutrheff Thematic
Biological validation

Nutraceuticals and foods of interest
Any, provided that they are thought to act by modulating a) (outside the brain) the inflammatory cascade and/or the oxidation-reduction pathway and/or the immunological system and/or b) have already been suggested/shown to influence the central nervous system. At present, we are analyzing the influence of an animal protein (present in the human everyday diet) on neuroinflammation, nociceptive transmission, cognitive functions and emotional states in mice. In particular, we are studying the effects of two different isoforms of that protein (here designed as X1, X2) that, following degradation by proteolysis, produce peptidic fragments showing distinct pharmacological properties. Preliminary results obtained in specific validated behavioral tests showed that when X1 or X2 isoforms are provided in the diet they significantly decrease memory functions, but do not affect anxious state. Diet enriched with X1, but not X2, also decreases the activation of microglia (the cells devoted to activity and immunological surveillance in the brain) in specific nuclei of the limbic system whereas CGRP (a neuropeptide involved in nociception and fear regulation) is unaffected. We also tested the two isoforms to evaluate their effect on the intestinal inflammation-induced modulation of neuroinflammation, nociceptive transmission and behavior. By using an established animal model, we first induced Inflammatory Bowel Disease (IBD) that induced increased anxiety in mice (without affecting memory functions) as well as decreased microglia activation and CGRP expression in specific nuclei of the limbic system. After IBD development, X1 or X2 diet decreases IBD-associated anxiety, with X2 diet decreasing also memory functions. In the limbic system, X1 diet rescues CGRP expression, but does not influence IBD-induced microglia activation. Instead, X2 diet rescues both IBD-induced CGRP expression and microglia activation state. The conclusion is that diet can profoundly alter cognitive and/or emotional state and these behavioral changes are accompanied by specific cellular and molecular alterations in nuclei of the limbic system, both in physiological and pathological conditions.

Fields of application
Nutrition and dietetics, human physiology, medical biochemistry, human nutrition and food science. Marketing and manufacturing of food, nutritional and bioactive natural products. Innovative foods treatment for neuroinflammation-related diseases. Promotion of quality of health. Nutraceuticals; nutraceutical market; nutraceutical industry; functional foods; functional ingredients; dietary supplements; health and nutritional supplements; biologically active phyto- and zoo-chemicals; medicinal and health foods; government agencies involved in developing regulatory guidelines; industrial scientists; health professionals; consumer groups.

Facilities and equipments
Accredited animal facility; fully equipped histological laboratory (including cryostat, confocal microscopes, equipment for immunohistochemistry, quantitative automatic image analysis and brain clarification); full array of behavioral tests for assessing memory, attentive and social skills, emotional state, stress and reward in rodents (including state-of-the-art equipment for assessing abuse liability of new compounds; touch-screen operant boxes for the determination of cognitive skills in rats; core battery safety pharmacology testing in both mice and rats)