“Progetti per avvio alla ricerca” - Type 1 for year 2018

Over the last decade, a close bidirectional relationship between metabolic and mood disorders has been demonstrated, suggesting the existence of a common pathophysiological route between these associated diseases. Interestingly, recent findings in animal models of metabolic diseases, such as obesity, type1 and type 2 diabetes mellitus, have shown that a long‐term high‐fat diet (HFD) elicits depressive‐like behaviours and promotes a complex alteration of the intestinal homeostasis, leading to a syndrome called “leaky gut”. This pathological condition was thus recognized as a potential involved event in the etiology of neurological disorders through the so-called “gut-brain axis”, a route of communication between the enteric nervous system (ENS) and the central nervous system (CNS). The idea of possible link between persistent intestinal milieu perturbation and mood disorders is fascinating but still elusive. Enteric glia cells (EGCs), a peripheral astrocytes-like cells that surround the enteric neurons in the ENS, have gained increasing attention because of their diverse emerging roles in the modulation of gut homeostasis. Conversely, activated glial cells play a key role in the progression of neuroinflammation in the ENS that it is not restricted in the intestinal milieu, but somehow, it may reverberates in the CNS. The present research aims at investigating the role of EGCs in leaky gut syndrome induced by HFD in mice, and particular it will evaluate: (1) if EGC-mediated neuroinflammatory response occurs following HFD-induced leaky gut and how it impacts on neuropathological changes within the ENS, (2) if EGC-activation is restricted at the intestinal level or it is associated with an ascending neuropathological signaling to the CNS, (3) to characterize the pathway(s) by which early leaky gut-induced ENS alteration propagates from the periphery to the brain, and finally (4) to correlate these events to anxiogenic/ depressive-like symptoms occurrence in mice.